microRNA - Knowledge

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microRNAs is comparable to that elsewhere in the non-coding DNA, implying evolution by neutral drift; however, older microRNAs have a much lower rate of change (often less than one substitution per hundred million years), suggesting that once a microRNA gains a function, it undergoes purifying selection. Individual regions within an miRNA gene face different evolutionary pressures, where regions that are vital for processing and function have higher levels of conservation. At this point, a microRNA is rarely lost from an animal's genome, although newer microRNAs (thus presumably non-functional) are frequently lost. In

704: 1537:, miRNA profiling of the FoxD1-derived cells not only comprehensively defined the transcriptional landscape of miRNAs that are critical for vascular development, but also identified key miRNAs that are likely to modulate the renal phenotype in its absence. These miRNAs include miRs‐10a, 18a, 19b, 24, 30c, 92a, 106a, 130a, 152, 181a, 214, 222, 302a, 370, and 381 that regulate Bcl2L11 (Bim) and miRs‐15b, 18a, 21, 30c, 92a, 106a, 125b‐5p, 145, 214, 222, 296‐5p and 302a that regulate p53-effector genes. Consistent with the profiling results, ectopic 5388: 1211: 57: 1398:. Furthermore, animal studies on specific miRNAs identified distinct roles for miRNAs both during heart development and under pathological conditions, including the regulation of key factors important for cardiogenesis, the hypertrophic growth response and cardiac conductance. Another role for miRNA in cardiovascular diseases is to use their expression levels for diagnosis, prognosis or risk stratification. miRNA's in animal models have also been linked to cholesterol metabolism and regulation. 532:. In this complex, DGCR8 orients the catalytic RNase III domain of Drosha to liberate hairpins from pri-miRNAs by cleaving RNA about eleven nucleotides from the hairpin base (one helical dsRNA turn into the stem). The product resulting has a two-nucleotide overhang at its 3' end; it has 3' hydroxyl and 5' phosphate groups. It is often termed as a pre-miRNA (precursor-miRNA). Sequence motifs downstream of the pre-miRNA that are important for efficient processing have been identified. 1374:, that bind the minor groove of AT-rich DNA stretches in specific regions of DNA. Human neoplasias, including thyroid, prostatic, cervical, colorectal, pancreatic and ovarian carcinomas, show a strong increase of HMGA1a and HMGA1b proteins. Transgenic mice with HMGA1 targeted to lymphoid cells develop aggressive lymphoma, showing that high HMGA1 expression is associated with cancers and that HMGA1 can act as an oncogene. HMGA2 protein specifically targets the promoter of 1417:(MMPs) are upregulated by d-flow, mediating pro-inflammatory and pro-angiogenic signals. These findings were observed in ligated carotid arteries of mice to mimic the effects of d-flow. Within 24 hours, pre-existing immature miR-712 formed mature miR-712 suggesting that miR-712 is flow-sensitive. Coinciding with these results, miR-712 is also upregulated in endothelial cells exposed to naturally occurring d-flow in the greater curvature of the aortic arch. 15738: 583: 468: 1900: 836: 390: 1617:, which results from blockage in the artery of the brain that carries oxygen-rich blood. The obstruction of the blood flow means the brain cannot receive necessary nutrients, such as oxygen and glucose, and remove wastes, such as carbon dioxide. miRNAs plays a role in posttranslational gene silencing by targeting genes in the pathogenesis of cerebral ischemia, such as the inflammatory, angiogenesis, and apoptotic pathway. 840:

on the degradation of mRNA. 40S and 60S are light and heavy components of the ribosome, 80S is the assembled ribosome bound to mRNA, eIF4F is a translation initiation factor, PABC1 is the Poly-A binding protein, and "cap" is the mRNA cap structure needed for mRNA circularization (which can be the normal m7G-cap or modified A-cap). The initiation of mRNA can proceed in a cap-independent manner, through recruiting 40S to IRES (

771:. It has been demonstrated that given complete complementarity between the miRNA and target mRNA sequence, Ago2 can cleave the mRNA and lead to direct mRNA degradation. In the absence of complementarity, silencing is achieved by preventing translation. The relation of miRNA and its target mRNA can be based on the simple negative regulation of a target mRNA, but it seems that a common scenario is the use of a "coherent 1160:. microRNA maturation can be inhibited at several points by steric-blocking oligos. The miRNA target site of an mRNA transcript can also be blocked by a steric-blocking oligo. For the "in situ" detection of miRNA, LNA or Morpholino probes can be used. The locked conformation of LNA results in enhanced hybridization properties and increases sensitivity and selectivity, making it ideal for detection of short miRNA. 640:. This endoribonuclease interacts with 5' and 3' ends of the hairpin and cuts away the loop joining the 3' and 5' arms, yielding an imperfect miRNA:miRNA* duplex about 22 nucleotides in length. Overall hairpin length and loop size influence the efficiency of Dicer processing. The imperfect nature of the miRNA:miRNA* pairing also affects cleavage. Some of the G-rich pre-miRNAs can potentially adopt the 368:) and "as" (antisense)). However, the mature microRNA found from one arm of the hairpin is usually much more abundant than that found from the other arm, in which case, an asterisk following the name indicates the mature species found at low levels from the opposite arm of a hairpin. For example, miR-124 and miR-124* share a pre-miRNA hairpin, but much more miR-124 is found in the cell. 46: 381:

shows that each has, on average, roughly 400 conserved targets. Likewise, experiments show that a single miRNA species can reduce the stability of hundreds of unique messenger RNAs. Other experiments show that a single miRNA species may repress the production of hundreds of proteins, but that this repression often is relatively mild (much less than 2-fold).

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refers to the mature form of the miRNA, while the uncapitalized "mir-" refers to the pre-miRNA and the pri-miRNA. The genes encoding miRNAs are also named using the same three-letter prefix according to the conventions of the organism gene nomenclature. For examples, the official miRNAs gene names in some organisms are "

574:(A to I) transitions. RNA editing can halt nuclear processing (for example, of pri-miR-142, leading to degradation by the ribonuclease Tudor-SN) and alter downstream processes including cytoplasmic miRNA processing and target specificity (e.g., by changing the seed region of miR-376 in the central nervous system). 1413:, a cardiovascular disease of the arterial wall associated with lipid retention and inflammation. Non-laminar blood flow also correlates with development of atherosclerosis as mechanosenors of endothelial cells respond to the shear force of disturbed flow (d-flow). A number of pro-atherogenic genes including 1832:, mice become more insulin-sensitive and remarkably resistant to high fat diet-induced obesity and diabetes. Not only could let-7 inhibition prevent obesity and diabetes, it could also reverse and cure the condition. These experimental findings suggest that let-7 inhibition could represent a new therapy for 700:

may also influence strand choice. The other strand, called the passenger strand due to its lower levels in the steady state, is denoted with an asterisk (*) and is normally degraded. In some cases, both strands of the duplex are viable and become functional miRNA that target different mRNA populations.

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miRNAs also play crucial roles in the regulation of complex enzymatic cascades including the hemostatic blood coagulation system. Large scale studies of functional miRNA targeting have recently uncovered rationale therapeutic targets in the hemostatic system. They have been directly linked to Calcium

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and functions to interact with the 5' end of the guide strand. They bind the mature miRNA and orient it for interaction with a target mRNA. Some argonautes, for example human Ago2, cleave target transcripts directly; argonautes may also recruit additional proteins to achieve translational repression.

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Dicer processing of the pre-miRNA is thought to be coupled with unwinding of the duplex. Generally, only one strand is incorporated into the miRISC, selected on the basis of its thermodynamic instability and weaker base-pairing on the 5' end relative to the other strand. The position of the stem-loop

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Estimates of the average number of unique messenger RNAs that are targets for repression by a typical miRNA vary, depending on the estimation method, but multiple approaches show that mammalian miRNAs can have many unique targets. For example, an analysis of the miRNAs highly conserved in vertebrates

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Under a standard nomenclature system, names are assigned to experimentally confirmed miRNAs before publication. The prefix "miR" is followed by a dash and a number, the latter often indicating order of naming. For example, miR-124 was named and likely discovered prior to miR-456. A capitalized "miR-"

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miRNAs are abundant in many mammalian cell types miRNAs appear to target about 60% of the genes of humans and other mammals. Many miRNAs are evolutionarily conserved, which implies that they have important biological functions. For example, 90 families of miRNAs have been conserved since at least the

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TIMP3 also decreases the expression of TNFα (a pro-inflammatory regulator) during turbulent flow. Activity of TNFα in turbulent flow was measured by the expression of TNFα-converting enzyme (TACE) in blood. TNFα decreased if miR-712 was inhibited or TIMP3 overexpressed, suggesting that miR-712

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While researchers focused on miRNA expression in physiological and pathological processes, various technical variables related to microRNA isolation emerged. The stability of stored miRNA samples has been questioned. microRNAs degrade much more easily than mRNAs, partly due to their length, but also

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Interaction of microRNA with protein translation process. Several translation repression mechanisms are shown: M1) on the initiation process, preventing assembling of the initiation complex or recruiting the 40S ribosomal subunit; M2) on the ribosome assembly; M3) on the translation process; M7, M8)

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enzymes, a modification that may be associated with miRNA degradation. However, uridylation may also protect some miRNAs; the consequences of this modification are incompletely understood. Uridylation of some animal miRNAs has been reported. Both plant and animal miRNAs may be altered by addition of

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Plant miRNAs usually have near-perfect pairing with their mRNA targets, which induces gene repression through cleavage of the target transcripts. In contrast, animal miRNAs are able to recognize their target mRNAs by using as few as 6–8 nucleotides (the seed region) at the 5' end of the miRNA, which

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RNAs, except their expression patterns were usually inconsistent with a role in regulating the timing of development. This suggested that most might function in other types of regulatory pathways. At this point, researchers started using the term "microRNA" to refer to this class of small regulatory

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Hepatocellular carcinoma cell proliferation may arise from miR-21 interaction with MAP2K3, a tumor repressor gene. Optimal treatment for cancer involves accurately identifying patients for risk-stratified therapy. Those with a rapid response to initial treatment may benefit from truncated treatment

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Turnover of mature miRNA is needed for rapid changes in miRNA expression profiles. During miRNA maturation in the cytoplasm, uptake by the Argonaute protein is thought to stabilize the guide strand, while the opposite (* or "passenger") strand is preferentially destroyed. In what has been called a

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Pre-miRNAs, pri-miRNAs and genes that lead to 100% identical mature miRNAs but that are located at different places in the genome are indicated with an additional dash-number suffix. For example, the pre-miRNAs hsa-mir-194-1 and hsa-mir-194-2 lead to an identical mature miRNA (hsa-miR-194) but are

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MicroRNAs have the potential to be used as tools or targets for treatment of different cancers. The specific microRNA, miR-506 has been found to work as a tumor antagonist in several studies. A significant number of cervical cancer samples were found to have downregulated expression of miR-506.

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Furthermore, specific miRNAs may be associated with certain histological subtypes of colorectal cancer. For instance, expression levels of miR-205 and miR-373 have been shown to be increased in mucinous colorectal cancers and mucin-producing Ulcerative Colitis-associated colon cancers, but not in

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The human homolog of miR-712 was found on the RN45s homolog gene, which maintains similar miRNAs to mice. MiR-205 of humans share similar sequences with miR-712 of mice and is conserved across most vertebrates. MiR-205 and miR-712 also share more than 50% of the cell signaling targets, including

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regions), but also by the duplication and modification of existing microRNAs. microRNAs can also form from inverted duplications of protein-coding sequences, which allows for the creation of a foldback hairpin structure. The rate of evolution (i.e. nucleotide substitution) in recently originated

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For partially complementary microRNAs to recognise their targets, nucleotides 2–7 of the miRNA (its 'seed region') must be perfectly complementary. Animal miRNAs inhibit protein translation of the target mRNA (this is present but less common in plants). Partially complementary microRNAs can also

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markers because of their apparently low rate of evolution. microRNAs' origin as a regulatory mechanism developed from previous RNAi machinery that was initially used as a defense against exogenous genetic material such as viruses. Their origin may have permitted the development of morphological

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Unlike plant microRNAs, the animal microRNAs target diverse genes. However, genes involved in functions common to all cells, such as gene expression, have relatively fewer microRNA target sites and seem to be under selection to avoid targeting by microRNAs. There is a strong correlation between

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miRNAs are considered to be key regulators of many developmental, homeostatic, and immune processes in plants. Their roles in plant development include shoot apical meristem development, leaf growth, flower formation, seed production, or root expansion. In addition, they play a complex role in

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fibers, providing the structural support and recoil properties of arteries. These fibers play a critical role in regulation of vascular inflammation and permeability, which are important in the development of atherosclerosis. Expressed by endothelial cells, TIMP3 is the only ECM-bound TIMP. A

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loop", "mutual negative feedback loop" (also termed double negative loop) and "positive feedback/feed-forward loop". Some miRNAs work as buffers of random gene expression changes arising due to stochastic events in transcription, translation and protein stability. Such regulation is typically

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in a number of diseases.Some researches show that mRNA cargo of exosomes may have a role in implantation, they can savage an adhesion between trophoblast and endometrium or support the adhesion by down regulating or up regulating expression of genes involved in adhesion/invasion.

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miRNA biogenesis in plants differs from animal biogenesis mainly in the steps of nuclear processing and export. Instead of being cleaved by two different enzymes, once inside and once outside the nucleus, both cleavages of the plant miRNA are performed by a Dicer homolog, called

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miRNAs can bind to target messenger RNA (mRNA) transcripts of protein-coding genes and negatively control their translation or cause mRNA degradation. It is of key importance to identify the miRNA targets accurately. A comparison of the predictive performance of eighteen

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Just as miRNA is involved in the normal functioning of eukaryotic cells, so has dysregulation of miRNA been associated with disease. A manually curated, publicly available database, miR2Disease, documents known relationships between miRNA dysregulation and human disease.

869:, causing mRNAs to be degraded sooner. While degradation of miRNA-targeted mRNA is well documented, whether or not translational repression is accomplished through mRNA degradation, translational inhibition, or a combination of the two is hotly debated. Recent work on 1058:, the net flux of miRNA genes has been predicted to be between 1.2 and 3.3 genes per million years. This makes them a valuable phylogenetic marker, and they are being looked upon as a possible solution to outstanding phylogenetic problems such as the relationships of 1862:

Viral microRNAs play an important role in the regulation of gene expression of viral and/or host genes to benefit the virus. Hence, miRNAs play a key role in host–virus interactions and pathogenesis of viral diseases. The expression of transcription activators by

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innovation, and by making gene expression more specific and 'fine-tunable', permitted the genesis of complex organs and perhaps, ultimately, complex life. Rapid bursts of morphological innovation are generally associated with a high rate of microRNA accumulation.

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The mature miRNA is part of an active RNA-induced silencing complex (RISC) containing Dicer and many associated proteins. RISC is also known as a microRNA ribonucleoprotein complex (miRNP); A RISC with incorporated miRNA is sometimes referred to as a "miRISC."

1230:(BCR) signalling, B-cell migration/adhesion, cell-cell interactions in immune niches and the production and class-switching of immunoglobulins. MiRNAs influence B cell maturation, generation of pre-, marginal zone, follicular, B1, plasma and memory B cells. 1460:

Anti-miR-712 effectively suppresses d-flow-induced miR-712 expression and increases TIMP3 expression. Anti-miR-712 also inhibits vascular hyperpermeability, thereby significantly reducing atherosclerosis lesion development and immune cell infiltration.

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The human genome encodes eight argonaute proteins divided by sequence similarities into two families: AGO (with four members present in all mammalian cells and called E1F2C/hAgo in humans), and PIWI (found in the germline and hematopoietic stem cells).

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is not enough pairing to induce cleavage of the target mRNAs. Combinatorial regulation is a feature of miRNA regulation in animals. A given miRNA may have hundreds of different mRNA targets, and a given target might be regulated by multiple miRNAs.

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proteins (HMGA1a, HMGA1b and HMGA2) are implicated in cancer, and expression of these proteins is regulated by microRNAs. HMGA expression is almost undetectable in differentiated adult tissues, but is elevated in many cancers. HMGA proteins are

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whereas plant miRNAs are usually complementary to coding regions of mRNAs. Perfect or near perfect base pairing with the target RNA promotes cleavage of the RNA. This is the primary mode of plant miRNAs. In animals the match-ups are imperfect.

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While the majority of miRNAs are located within the cell, some miRNAs, commonly known as circulating miRNAs or extracellular miRNAs, have also been found in extracellular environment, including various biological fluids and cell culture media.

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The first miRNA was discovered in the early 1990s. However, miRNAs were not recognized as a distinct class of biological regulators until the early 2000s. miRNA research revealed different sets of miRNAs expressed in different cell types and

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gene, which reduces protein expression of MGMT. However, for 28% of glioblastomas, the MGMT protein is deficient, but the MGMT promoter is not methylated. In glioblastomas without methylated MGMT promoters, the level of microRNA miR-181d is

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sporadic colonic adenocarcinoma that lack mucinous components. In-vitro studies suggested that miR-205 and miR-373 may functionally induce different features of mucinous-associated neoplastic progression in intestinal epithelial cells.

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heart. This revealed that miRNAs play an essential role during its development. miRNA expression profiling studies demonstrate that expression levels of specific miRNAs change in diseased human hearts, pointing to their involvement in

673:(DL1). DL1 is expressed only in the nucleus of plant cells, which indicates that both reactions take place inside the nucleus. Before plant miRNA:miRNA* duplexes are transported out of the nucleus, its 3' overhangs are methylated by a 1103:

Across all species, in excess of 5000 different miRNAs had been identified by March 2010. Whilst short RNA sequences (50 – hundreds of base pairs) of a broadly comparable function occur in bacteria, bacteria lack true microRNAs.

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are thought to be a back channel of communication regulating expression levels between paralogous genes (genes having a similar structure indicating divergence from a common ancestral gene). Given the name "competing endogenous RNAs"

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decrease in TIMP3 expression results in an increase of ECM degradation in the presence of d-flow. Consistent with these findings, inhibition of pre-miR712 increases expression of TIMP3 in cells, even when exposed to turbulent flow.

1140:, slides or chips with probes to hundreds or thousands of miRNA targets, so that relative levels of miRNAs can be determined in different samples. microRNAs can be both discovered and profiled by high-throughput sequencing methods ( 1257:

regimens, showing the value of accurate disease response measures. Cell-free circulating miRNAs (cimiRNAs) are highly stable in blood, are overexpressed in cancer and are quantifiable within the diagnostic laboratory. In classical

12731:"Activation of CCAAT/enhancer-binding protein (C/EBP) alpha expression by C/EBP beta during adipogenesis requires a peroxisome proliferator-activated receptor-gamma-associated repression of HDAC1 at the C/ebp alpha gene promoter" 844:) located in 5'UTR region. The actual work of RNA silencing is performed by RISC in which the main catalytic subunit is one of the Argonaute proteins (AGO), and miRNA serves as a template for recognizing specific mRNA sequences. 1175:- and miRNA-data that predict miRNA-targets based on their base sequence. While this is usually done after miRNAs of interest have been detected (e. g. because of high expression levels), ideas for analysis tools that integrate 715:(Ago) protein family are central to RISC function. Argonautes are needed for miRNA-induced silencing and contain two conserved RNA binding domains: a PAZ domain that can bind the single stranded 3' end of the mature miRNA and a 801:, also known as Rat1p. In plants, SDN (small RNA degrading nuclease) family members degrade miRNAs in the opposite (3'-to-5') direction. Similar enzymes are encoded in animal genomes, but their roles have not been described. 762:

Gene silencing may occur either via mRNA degradation or preventing mRNA from being translated. For example, miR16 contains a sequence complementary to the AU-rich element found in the 3'UTR of many unstable mRNAs, such as

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Skårn M, Namløs HM, Noordhuis P, Wang MY, Meza-Zepeda LA, Myklebost O (April 2012). "Adipocyte differentiation of human bone marrow-derived stromal cells is modulated by microRNA-155, microRNA-221, and microRNA-222".

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Lee CT, Risom T, Strauss WM (April 2007). "Evolutionary conservation of microRNA regulatory circuits: an examination of microRNA gene complexity and conserved microRNA-target interactions through metazoan phylogeny".

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of alcohol-dependent mice, suggesting the role of miRNA in orchestrating translational imbalances and the creation of differentially expressed proteins within an area of the brain where complex cognitive behavior and

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When two mature microRNAs originate from opposite arms of the same pre-miRNA and are found in roughly similar amounts, they are denoted with a -3p or -5p suffix. (In the past, this distinction was also made with "s"

1637:. miRNA global regulation of many downstream genes deems significant regarding the reorganization or synaptic connections or long term neural adaptations involving the behavioral change from alcohol consumption to 411:), the site-specific modification of RNA sequences to yield products different from those encoded by their DNA. This increases the diversity and scope of miRNA action beyond that implicated from the genome alone. 512:

A single pri-miRNA may contain from one to six miRNA precursors. These hairpin loop structures are composed of about 70 nucleotides each. Each hairpin is flanked by sequences necessary for efficient processing.

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Mencía A, Modamio-Høybjør S, Redshaw N, Morín M, Mayo-Merino F, Olavarrieta L, et al. (May 2009). "Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss".

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and multiple roles for miRNAs in plant and animal development and in many other biological processes. Aberrant miRNA expression are implicated in disease states. MiRNA-based therapies are under investigation.

681:(HEN1). The duplex is then transported out of the nucleus to the cytoplasm by a protein called Hasty (HST), an Exportin 5 homolog, where they disassemble and the mature miRNA is incorporated into the RISC. 8132:"Draft genome assemblies and predicted microRNA complements of the intertidal lophotrochozoans Patella vulgata (Mollusca, Patellogastropoda) and Spirobranchus (Pomatoceros) lamarcki (Annelida, Serpulida)" 152:

common ancestor of mammals and fish, and most of these conserved miRNAs have important functions, as shown by studies in which genes for one or more members of a family have been knocked out in mice.

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that in turn forms part of a several hundred nucleotide-long miRNA precursor termed a pri-miRNA. When a stem-loop precursor is found in the 3' UTR, a transcript may serve as a pri-miRNA and a mRNA.

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Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, et al. (November 2000). "Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA".

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Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, et al. (February 2000). "The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans".

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miRNAs with nearly identical sequences except for one or two nucleotides are annotated with an additional lower case letter. For example, miR-124a is closely related to miR-124b. For example:

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Sgarra R, Rustighi A, Tessari MA, Di Bernardo J, Altamura S, Fusco A, et al. (September 2004). "Nuclear phosphoproteins HMGA and their relationship with chromatin structure and cancer".

1378:, thus reducing expression of this DNA repair gene. ERCC1 protein expression was deficient in 100% of 47 evaluated colon cancers (though the extent to which HGMA2 was involved is not known). 4145:

Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. (February 2005). "Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs".

616:, recognizes a two-nucleotide overhang left by the RNase III enzyme Drosha at the 3' end of the pre-miRNA hairpin. Exportin-5-mediated transport to the cytoplasm is energy-dependent, using 7954:

Allen E, Xie Z, Gustafson AM, Sung GH, Spatafora JW, Carrington JC (December 2004). "Evolution of microRNA genes by inverted duplication of target gene sequences in Arabidopsis thaliana".

1062:. On the other hand, in multiple cases microRNAs correlate poorly with phylogeny, and it is possible that their phylogenetic concordance largely reflects a limited sampling of microRNAs. 1028:

in both plants and animals, and are thought to be a vital and evolutionarily ancient component of gene regulation. While core components of the microRNA pathway are conserved between

11774:"Long-term potentiation and depression regulatory microRNAs were highlighted in Bisphenol A induced learning and memory impairment by microRNA sequencing and bioinformatics analysis" 1681:) and ultimately reducing its expression. BDNF plays a critical role in the formation and maturation of new neurons and synapses, suggesting a possible implication in synapse growth/ 785:"Use it or lose it" strategy, Argonaute may preferentially retain miRNAs with many targets over miRNAs with few or no targets, leading to degradation of the non-targeting molecules. 1261:, plasma miR-21, miR-494, and miR-1973 are promising disease response biomarkers. Circulating miRNAs have the potential to assist clinical decision making and aid interpretation of 11151:

Yang B, Lin H, Xiao J, Lu Y, Luo X, Li B, et al. (April 2007). "The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2".

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It is often impossible to discern these mechanisms using experimental data about stationary reaction rates. Nevertheless, they are differentiated in dynamics and have different

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Kaur H, Arora A, Wengel J, Maiti S (June 2006). "Thermodynamic, counterion, and hydration effects for the incorporation of locked nucleic acid nucleotides into DNA duplexes".

1928: 1923: 1777:, have been found during the adipogenic programming of both immortalized and primary hMSCs, suggesting that they act as negative regulators of differentiation. Conversely, 1641:

and/or dependence. Up to 35 different miRNAs have been found to be altered in the alcoholic post-mortem brain, all of which target genes that include the regulation of the

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Boeckel JN, Reis SM, Leistner D, Thomé CE, Zeiher AM, Fichtlscherer S, et al. (April 2014). "From heart to toe: heart's contribution on peripheral microRNA levels".

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to the animals. However, the difference in how these microRNAs function and the way they are processed suggests that microRNAs arose independently in plants and animals.

423:(Pol II). The polymerase often binds to a promoter found near the DNA sequence, encoding what will become the hairpin loop of the pre-miRNA. The resulting transcript is 1381:

Single Nucleotide polymorphisms (SNPs) can alter the binding of miRNAs on 3'UTRs for example the case of hsa-mir181a and hsa-mir181b on the CDON tumor suppressor gene.

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gene. However, up to 15% of MLH1-deficiencies in sporadic colon cancers appeared to be due to over-expression of the microRNA miR-155, which represses MLH1 expression.

1289:. A new strategy for tumor treatment is to inhibit tumor cell proliferation by repairing the defective miRNA pathway in tumors. Cancer is caused by the accumulation of 3053:

Wienholds E, Kloosterman WP, Miska E, Alvarez-Saavedra E, Berezikov E, de Bruijn E, et al. (July 2005). "MicroRNA expression in zebrafish embryonic development".

962:. dsRNAs targeting gene promoters can induce potent transcriptional activation of associated genes. This was demonstrated in human cells using synthetic dsRNAs termed 810:(thale cress), mature plant miRNAs appear to be stabilized by the addition of methyl moieties at the 3' end. The 2'-O-conjugated methyl groups block the addition of 3224:

Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, et al. (November 2004). "A pancreatic islet-specific microRNA regulates insulin secretion".

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According to the Center for Disease Control and Prevention, Stroke is one of the leading causes of death and long-term disability in America. 87% of the cases are

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MicroRNA-21 promotes hepatocellular carcinoma HepG2 cell proliferation through repression of mitogen-activated protein kinase-kinase 3. Guangxian Xu et al., 2013

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van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN (April 2007). "Control of stress-dependent cardiac growth and gene expression by a microRNA".

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was observed in the cellular derivatives of the FoxD1 derived progenitor lineage and reiterates the importance of renal stromal miRNAs in cellular homeostasis.

1533:. p53 protein levels remained unchanged, suggesting that FoxD1 stromal miRNAs directly repress p53-effector genes. Using a lineage tracing approach followed by 136:

pathway, except miRNAs derive from regions of RNA transcripts that fold back on themselves to form short hairpins, whereas siRNAs derive from longer regions of

1824:. When let-7 was ectopically overexpressed to mimic accelerated aging, mice became insulin-resistant, and thus more prone to high fat diet-induced obesity and 1444:(TIMP3). TIMPs normally regulate activity of matrix metalloproteinases (MMPs) which degrade the extracellular matrix (ECM). Arterial ECM is mainly composed of 1888:

algorithms is available. Large scale studies of functional miRNA targeting suggest that many functional miRNAs can be missed by target prediction algorithms.

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When tested, d-flow decreased the expression of XRN1 in humans as it did in mice endothelial cells, indicating a potentially common role of XRN1 in humans.

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Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N (September 2008). "Widespread changes in protein synthesis induced by microRNAs".

9132:"Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis" 9698:"MicroRNAs and the Diagnosis of Childhood Acute Lymphoblastic Leukemia: Systematic Review, Meta-Analysis and Re-Analysis with Novel Small RNA-Seq Tools" 1359:

of MGMT mRNA). Thus, in 28% of glioblastomas, increased expression of miR-181d and reduced expression of DNA repair enzyme MGMT may be a causal factor.

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of other genes. These are usually, though not exclusively, found in a sense orientation, and thus usually are regulated together with their host genes.

13782: 8376: 1553:. Previous studies demonstrate that miRNAs can regulate neuronal differentiation and maturation at various stages. MiRNAs also play important roles in 3338:"Energizing miRNA research: a review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways" 1047:

New microRNAs are created in multiple ways. Novel microRNAs can originate from the random formation of hairpins in "non-coding" sections of DNA (i.e.

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Lau NC, Lim LP, Weinstein EG, Bartel DP (October 2001). "An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans".

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of ~100 amino acid residues characterized by a modular sequence organization. These proteins have three highly positively charged regions, termed

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Additionally, miR-506 works to promote apoptosis of cervical cancer cells, through its direct target hedgehog pathway transcription factor, Gli3.

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Zhao Y, Samal E, Srivastava D (July 2005). "Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis".

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responses to various abiotic stresses comprising heat stress, low-temperature stress, drought stress, light stress, or gamma radiation exposure.

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cases. However, altered expression of microRNAs, causing DNA repair deficiencies, are frequently associated with cancers and may be an important

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Winter J, Jung S, Keller S, Gregory RI, Diederichs S (March 2009). "Many roads to maturity: microRNA biogenesis pathways and their regulation".

5787:"Structural features of microRNA (miRNA) precursors and their relevance to miRNA biogenesis and small interfering RNA/short hairpin RNA design" 1677:

expression increased in the prefrontal cortex of alcohol-dependent rats, targeting the transcription factor brain-derived neurotrophic factor (

11116: 10610:"High mobility group A2 protein and its derivatives bind a specific region of the promoter of DNA repair gene ERCC1 and modulate its activity" 10477:"O6-Methylguanine DNA methyltransferase protein expression in tumor cells predicts outcome of temozolomide therapy in glioblastoma patients" 3544:

Fasanaro P, Greco S, Ivan M, Capogrossi MC, Martelli F (January 2010). "microRNA: emerging therapeutic targets in acute ischemic diseases".

3144:"bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila" 982:), these microRNAs bind to "microRNA response elements" on genes and pseudogenes and may provide another explanation for the persistence of 8326:"MicroRNAs and essential components of the microRNA processing machinery are not encoded in the genome of the ctenophore Mnemiopsis leidyi" 7109: 1721:

that ultimately result in addictive behaviors. Alternatively, overexpressing miR-382 resulted in attenuated drinking and the inhibition of

144:

may encode over 1900 miRNAs, However, only about 500 human miRNAs represent bona fide miRNAs in the manually curated miRNA gene database

13297:

Wong CE, Zhao YT, Wang XJ, Croft L, Wang ZH, Haerizadeh F, et al. (May 2011). "MicroRNAs in the shoot apical meristem of soybean".

4786:

Gregory RI, Chendrimada TP, Shiekhattar R (2006). "MicroRNA biogenesis: isolation and characterization of the microprocessor complex".

4735:

Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. (September 2003). "The nuclear RNase III Drosha initiates microRNA processing".

10569:"The HMG-I oncogene causes highly penetrant, aggressive lymphoid malignancy in transgenic mice and is overexpressed in human leukemia" 6220: 494:

domains (blue and orange); a double-stranded RNA binding domain (yellow); and a connector/platform domain (gray) containing two bound

14112: 776:

achieved by the virtue of negative feedback loops or incoherent feed-forward loop uncoupling protein output from mRNA transcription.

11194:

Carè A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, et al. (May 2007). "MicroRNA-133 controls cardiac hypertrophy".

7752:

Wheeler BM, Heimberg AM, Moy VN, Sperling EA, Holstein TW, Heber S, et al. (2009). "The deep evolution of metazoan microRNAs".

2880:

Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (October 2001). "Identification of novel genes coding for small expressed RNAs".

652:. Although either strand of the duplex may potentially act as a functional miRNA, only one strand is usually incorporated into the 10047:"miR-506 acts as a tumor suppressor by directly targeting the hedgehog pathway transcription factor Gli3 in human cervical cancer" 15333: 1343: 12374:"Coordinated dysregulation of mRNAs and microRNAs in the rat medial prefrontal cortex following a history of alcohol dependence" 11415:"The atypical mechanosensitive microRNA-712 derived from pre-ribosomal RNA induces endothelial inflammation and atherosclerosis" 1429:

region 2 (ITS2). XRN1 is an exonuclease that degrades the ITS2 region during processing of RN45s. Reduction of XRN1 under d-flow

1301:

cause the accumulation of mutations, which can lead to cancer. Several genes involved in DNA repair are regulated by microRNAs.

15071: 13841: 13775: 4050:

Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, et al. (May 2005). "Combinatorial microRNA target predictions".

173:

and including Lee and Feinbaum. However, additional insight into its mode of action required simultaneously published work by

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Caravas J, Friedrich M (June 2010). "Of mites and millipedes: recent progress in resolving the base of the arthropod tree".

6322:

Chatterjee S, Grosshans H (September 2009). "Active turnover modulates mature microRNA activity in Caenorhabditis elegans".

3632:"Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans" 1171:-expression is therefore often analyzed to check for miRNA-effects in their levels (e.g. in). Databases can be used to pair 11345:

Insull W (January 2009). "The pathology of atherosclerosis: plaque development and plaque responses to medical treatment".

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RNA and additional "small temporal RNAs" might regulate the timing of development in diverse animals, including humans.

14987: 12593:"MicroRNA expression profile and functional analysis reveal that miR-382 is a critical novel gene of alcohol addiction" 11833:"Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration" 9998:"MiR-506 suppresses proliferation and induces senescence by directly targeting the CDK4/6-FOXM1 axis in ovarian cancer" 9749:"Identification of miR-374a as a prognostic marker for survival in patients with early-stage nonsmall cell lung cancer" 9639:"A comprehensive investigation of histotype-specific microRNA and their variants in Stage I epithelial ovarian cancers" 1534: 456: 12423:"Integration of miRNA and protein profiling reveals coordinated neuroadaptations in the alcohol-dependent mouse brain" 1389:

The global role of miRNA function in the heart has been addressed by conditionally inhibiting miRNA maturation in the

201:, one of which was a ~22-nucleotide RNA that contained sequences partially complementary to multiple sequences in the 15419: 14982: 14977: 14972: 14967: 14962: 14957: 14952: 14947: 14942: 14937: 14932: 14927: 14922: 14917: 14912: 14907: 14902: 14897: 14892: 14887: 14882: 14877: 14872: 14867: 14862: 14857: 14852: 14847: 14842: 14837: 14832: 14827: 14822: 14817: 14812: 14807: 14802: 14797: 14781: 14776: 14771: 14766: 14761: 14756: 14751: 14746: 14741: 14736: 14731: 14726: 14721: 14716: 14711: 14706: 14701: 14696: 14691: 14686: 14681: 14676: 14671: 14666: 14650: 14645: 14640: 14635: 14630: 14625: 14620: 14615: 14610: 14605: 14600: 14595: 14585: 14580: 14575: 14570: 14560: 14555: 14550: 14545: 14540: 14535: 14530: 14514: 14509: 14504: 14499: 14494: 14489: 14484: 14479: 14474: 14469: 14464: 14459: 14454: 14449: 14444: 14439: 14434: 14429: 14424: 14419: 14414: 14409: 14399: 14394: 14389: 14384: 14379: 14374: 14369: 14353: 14343: 14338: 14333: 14328: 14323: 14318: 14313: 14293: 14288: 14283: 14243: 14217: 14212: 14207: 14202: 14187: 14182: 14177: 14172: 14167: 14152: 14142: 14127: 14122: 14072: 14062: 14052: 14047: 14032: 14017: 13768: 12967:"Large-scale identification of functional microRNA targeting reveals cooperative regulation of the hemostatic system" 12024: 8800:"Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development" 1036:, miRNA repertoires in the two kingdoms appear to have emerged independently with different primary modes of action. 870: 516:

The double-stranded RNA (dsRNA) structure of the hairpins in a pri-miRNA is recognized by a nuclear protein known as

9281:"MicroRNA and mRNA integrated analysis (MMIA): a web tool for examining biological functions of microRNA expression" 15706: 15177: 13996: 13991: 13986: 13981: 13976: 13971: 13966: 13961: 13946: 13941: 13931: 13911: 13906: 13901: 13896: 13891: 13876: 13871: 13866: 13861: 13856: 13851: 13846: 10708:

Gibert B, Delloye-Bourgeois C, Gattolliat CH, Meurette O, Le Guernevel S, Fombonne J, et al. (November 2014).

2579:"Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets" 1958: 1241:

a levels may serve as an indicator of poor survival. Either high miR-185 or low miR-133b levels may correlate with

15711: 15105: 13821: 13816: 13806: 1356: 9048:"Revealing details: whole mount microRNA in situ hybridization protocol for zebrafish embryos and adult tissues" 3275:

Chen CZ, Li L, Lodish HF, Bartel DP (January 2004). "MicroRNAs modulate hematopoietic lineage differentiation".

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Chen K, Rajewsky N (February 2007). "The evolution of gene regulation by transcription factors and microRNAs".

1485:-derived renal progenitor cells in a murine model resulted in a complex renal phenotype including expansion of 13095:"Programming pluripotent precursor cells derived from Xenopus embryos to generate specific tissues and organs" 7341:"A genome-wide microRNA screen identifies the microRNA-183/96/182 cluster as a modulator of circadian rhythms" 15608: 15494: 2674:"A Uniform System for the Annotation of Vertebrate microRNA Genes and the Evolution of the Human microRNAome" 1234: 690: 653: 84: 10475:

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Rana TM (January 2007). "Illuminating the silence: understanding the structure and function of small RNAs".

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Jonas S, Izaurralde E (July 2015). "Towards a molecular understanding of microRNA-mediated gene silencing".

2202:

Jonas S, Izaurralde E (July 2015). "Towards a molecular understanding of microRNA-mediated gene silencing".

644:

structure as an alternative to the canonical stem-loop structure. For example, human pre-miRNA 92b adopts a

9796:"miR-185 and miR-133b deregulation is associated with overall survival and metastasis in colorectal cancer" 7602:"MicroRNAs and metazoan macroevolution: insights into canalization, complexity, and the Cambrian explosion" 1633:. Chronic alcohol abuse results in persistent changes in brain function mediated in part by alterations in 1561:(contributing to learning and memory). Elimination of miRNA formation in mice by experimental silencing of 1262: 1219: 841: 13725: 12531:"Chronic alcohol-induced microRNA-155 contributes to neuroinflammation in a TLR4-dependent manner in mice" 11933:"Role of miRNAs in Neurodegeneration: From Disease Cause to Tools of Biomarker Discovery and Therapeutics" 11058:"MicroRNA miR-133 represses HERG K+ channel expression contributing to QT prolongation in diabetic hearts" 1845:

homeostasis in the endoplasmic reticulum, which is critical in cell differentiation in early development.

1136:. Variations of this method achieve absolute or relative quantification. miRNAs can also be hybridized to 882: 15721: 15716: 15701: 15326: 13412:"Small RNA deep sequencing identifies microRNAs and other small noncoding RNAs from human herpesvirus 6B" 12770:

Jun-Hao ET, Gupta RR, Shyh-Chang N (March 2016). "Lin28 and let-7 in the Metabolic Physiology of Aging".

10899:"A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure" 10710:"Regulation by miR181 family of the dependence receptor CDON tumor suppressive activity in neuroblastoma" 8131: 1913: 1638: 1426: 935:

Transcriptional inhibition through microRNA-mediated chromatin reorganization followed by gene silencing.

764: 11629:"MicroRNAs: Key Regulators in the Central Nervous System and Their Implication in Neurological Diseases" 6928:"Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution" 4526:"Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes" 407:

The DNA template is not the final word on mature miRNA production: 6% of human miRNAs show RNA editing (

49:

Pre-miRNA instead of Pri-miRNA in the first point of mechanism. Diagram of microRNA (miRNA) action with

15064: 14222: 14157: 14147: 14137: 4379:"Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs" 3912: 3910: 3908: 1565:

has led to pathological outcomes, such as reduced neuronal size, motor abnormalities (when silenced in

1514: 1505:

profiling of the FoxD1-Dicer knockout mouse model revealed ectopic upregulation of pro-apoptotic gene,

608:

Pre-miRNA hairpins are exported from the nucleus in a process involving the nucleocytoplasmic shuttler

11890:

Hébert SS, Papadopoulou AS, Smith P, Galas MC, Planel E, Silahtaroglu AN, et al. (October 2010).

8551:

Shingara J, Keiger K, Shelton J, Laosinchai-Wolf W, Powers P, Conrad R, et al. (September 2005).

6524:"Deep sequencing of tomato short RNAs identifies microRNAs targeting genes involved in fruit ripening" 5222:

Kawahara Y, Megraw M, Kreider E, Iizasa H, Valente L, Hatzigeorgiou AG, et al. (September 2008).

13921: 13916: 13659:"The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14" 10608:

Borrmann L, Schwanbeck R, Heyduk T, Seebeck B, Rogalla P, Bullerdiek J, et al. (December 2003).

7795:

Pashkovskiy PP, Ryazansky SS (June 2013). "Biogenesis, evolution, and functions of plant microRNAs".

4960:"Beyond secondary structure: primary-sequence determinants license pri-miRNA hairpins for processing" 2728:"The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14" 1594: 1199:

A mutation in the seed region of miR-184 causes hereditary keratoconus with anterior polar cataract.

1125: 11982:

Henshall DC, Hamer HM, Pasterkamp RJ, Goldstein DB, Kjems J, Prehn JH, et al. (December 2016).

10897:

van Rooij E, Sutherland LB, Liu N, Williams AH, McAnally J, Gerard RD, et al. (November 2006).

7483: 6771:"miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay" 5387: 3905: 15767: 15290: 15033: 15028: 13831: 13826: 13811: 8038:

Fahlgren N, Jogdeo S, Kasschau KD, Sullivan CM, Chapman EJ, Laubinger S, et al. (April 2010).

6522:

Moxon S, Jing R, Szittya G, Schwach F, Rusholme Pilcher RL, Moulton V, et al. (October 2008).

3387:"The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb" 2422:

Fromm B, Domanska D, Høye E, Ovchinnikov V, Kang W, Aparicio-Puerta E, et al. (January 2020).

1817: 1414: 827:, stabilizes the molecule and plant miRNAs ending with an adenine residue have slower decay rates. 356:) miRNA. Other common prefixes include "v" for viral (miRNA encoded by a viral genome) and "d" for 226: 179: 7290:

Cuman C, Van Sinderen M, Gantier MP, Rainczuk K, Sorby K, Rombauts L, et al. (October 2015).

6714:"Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish" 15777: 8459:

Liu CG, Calin GA, Volinia S, Croce CM (2008). "MicroRNA expression profiling using microarrays".

8275:

Ryan JF, Pang K, Schnitzler CE, Nguyen AD, Moreland RT, Simmons DK, et al. (December 2013).

1582: 1266: 432: 13344:"VIRmiRNA: a comprehensive resource for experimentally validated viral miRNAs and their targets" 11290:"Improved risk stratification in prevention by use of a panel of selected circulating microRNAs" 9480:

Hughes AE, Bradley DT, Campbell M, Lechner J, Dash DP, Simpson DA, et al. (November 2011).

3107:

Jones-Rhoades MW, Bartel DP, Bartel B (2006). "MicroRNAS and their regulatory roles in plants".

2101:"VIRmiRNA: a comprehensive resource for experimentally validated viral miRNAs and their targets" 1729:

upregulation in rat models of alcoholism, demonstrating the possibility of using miRNA-targeted

15741: 15434: 15319: 15115: 12372:

Tapocik JD, Solomon M, Flanigan M, Meinhardt M, Barbier E, Schank JR, et al. (June 2013).

11475:"Loss of Timp3 gene leads to abdominal aortic aneurysm formation in response to angiotensin II" 7478: 7251:"Circulating microRNAs as potential biomarkers for psychiatric and neurodegenerative disorders" 6168:

Meister G, Landthaler M, Peters L, Chen PY, Urlaub H, Lührmann R, et al. (December 2005).

5785:

Krol J, Sobczak K, Wilczynska U, Drath M, Jasinska A, Kaczynska D, et al. (October 2004).

3002:

Lee RC, Ambros V (October 2001). "An extensive class of small RNAs in Caenorhabditis elegans".

1750: 1578: 1574: 1324: 804:

Several miRNA modifications affect miRNA stability. As indicated by work in the model organism

790: 772: 617: 529: 185: 17: 11580:"Renal stromal miRNAs are required for normal nephrogenesis and glomerular mesangial survival" 10817:"Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2" 5959:"The long and short of inverted repeat genes in animals: microRNAs, mirtrons and hairpin RNAs" 1226:". In malignant B cells miRNAs participate in pathways fundamental to B cell development like 1222:. Many other miRNAs also have links with cancer and accordingly are sometimes referred to as " 1163:

High-throughput quantification of miRNAs is error prone, for the larger variance (compared to

15618: 15462: 15207: 15057: 13739: 12813:

Zhu H, Shyh-Chang N, Segrè AV, Shinoda G, Shah SP, Einhorn WS, et al. (September 2011).

12482:"microRNA-206 in rat medial prefrontal cortex regulates BDNF expression and alcohol drinking" 12480:

Tapocik JD, Barbier E, Flanigan M, Solomon M, Pincus A, Pilling A, et al. (March 2014).

9330:"Detection of simultaneous group effects in microRNA expression and related target gene sets" 8942:"Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430" 8842: 8277:"The genome of the ctenophore Mnemiopsis leidyi and its implications for cell type evolution" 4298: 3120: 2361: 1968: 903:

Nine mechanisms of miRNA action are described and assembled in a unified mathematical model:

743:(FMRP), Tudor staphylococcal nuclease-domain-containing protein (Tudor-SN), the putative DNA 472: 129: 118: 13047:

Berardi E, Pues M, Thorrez L, Sampaolesi M (October 2012). "miRNAs in ESC differentiation".

9794:

Akçakaya P, Ekelund S, Kolosenko I, Caramuta S, Ozata DM, Xie H, et al. (August 2011).

9529:

de Pontual L, Yao E, Callier P, Faivre L, Drouin V, Cariou S, et al. (September 2011).

7999:"Comparative analysis of the MIR319a microRNA locus in Arabidopsis and related Brassicaceae" 6119:

Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, et al. (March 2002).

3951: 1269:. They can be performed at each consultation to assess disease response and detect relapse. 15653: 15636: 15467: 15197: 13204: 12875: 12542: 12434: 12095: 11844: 11785: 11533: 11426: 11301: 11288:

Keller T, Boeckel JN, Groß S, Klotsche J, Palapies L, Leistner D, et al. (July 2017).

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Valeri N, Gasparini P, Fabbri M, Braconi C, Veronese A, Lovat F, et al. (April 2010).

9851: 9591: 9578:

Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, et al. (August 2004).

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Lim LP, Lau NC, Weinstein EG, Abdelhakim A, Yekta S, Rhoades MW, et al. (April 2003).

2301: 1879:

List of RNA structure prediction software § Inter molecular interactions: MicroRNA:UTR

1722: 1710: 1348: 1092: 1054: 963: 806: 13566:

Ambros V, Bartel B, Bartel DP, Burge CB, Carrington JC, Chen X, et al. (March 2003).

10956:

Tatsuguchi M, Seok HY, Callis TE, Thomson JM, Chen JF, Newman M, et al. (June 2007).

10659:"Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer" 10323:"Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer" 10321:

Truninger K, Menigatti M, Luz J, Russell A, Haider R, Gebbers JO, et al. (May 2005).

6663:

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5539:"A potassium ion-dependent RNA structural switch regulates human pre-miRNA 92b maturation" 3712:

Ambros V, Bartel B, Bartel DP, Burge CB, Carrington JC, Chen X, et al. (March 2003).

2910: 2354: 819:

adenine (A) residues to the 3' end of the miRNA. An extra A added to the end of mammalian

348:

Species of origin is designated with a three-letter prefix, e.g., hsa-miR-124 is a human (

197:

miRNA, they found that instead of producing an mRNA encoding a protein, it produced short

8: 15648: 15631: 15489: 15372: 15187: 15136: 13195:

Choudhary A, Kumar A, Kaur H, Kaur N (May 2021). "MiRNA: the taskmaster of plant world".

12864:"Control of glucose homeostasis and insulin sensitivity by the Let-7 family of microRNAs" 10750: 9531:"Germline deletion of the miR-17~92 cluster causes skeletal and growth defects in humans" 8553:"An optimized isolation and labeling platform for accurate microRNA expression profiling" 6967:

He L, Hannon GJ (July 2004). "MicroRNAs: small RNAs with a big role in gene regulation".

6828:"Transcriptional inhibiton of Hoxd4 expression by miRNA-10a in human breast cancer cells" 5352: 1978: 1938: 1865: 1730: 1682: 1573:

neurons). Altered miRNA expression has been found in neurodegenerative diseases (such as

1558: 1316: 1145: 1141: 997: 563: 137: 13208: 12879: 12546: 12438: 12100: 12082:

Feng J, Sun G, Yan J, Noltner K, Li W, Buzin CH, et al. (July 2009). Reif A (ed.).

11848: 11831:

Cuellar TL, Davis TH, Nelson PT, Loeb GB, Harfe BD, Ullian E, et al. (April 2008).

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Facista A, Nguyen H, Lewis C, Prasad AR, Ramsey L, Zaitlin B, et al. (April 2012).

10426:

Zhang W, Zhang J, Hoadley K, Kushwaha D, Ramakrishnan V, Li S, et al. (June 2012).

10379: 9855: 9595: 9580:"MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias" 9345: 8957: 8194: 8179:"The Ectocarpus genome and the independent evolution of multicellularity in brown algae" 8147: 7858: 7356: 7058: 6786: 6729: 6632: 6607: 6429:"Prediction and identification of Arabidopsis thaliana microRNAs and their mRNA targets" 6335: 6185: 6077: 5130: 5073: 4748: 4644: 4264: 4209: 4158: 3472: 3445: 3402: 3288: 3237: 3066: 3015: 2959: 2893: 2837: 2783: 2689: 2540: 2305: 1717:, a transcription factor that activates a series of transcription events in the nucleus 15542: 15537: 15412: 15217: 15212: 13751: 13640: 13592: 13567: 13538: 13511: 13487: 13460: 13436: 13411: 13368: 13343: 13274: 13247: 13228: 13172: 13145: 13121: 13094: 13072: 12898: 12863: 12839: 12814: 12795: 12665: 12617: 12592: 12565: 12530: 12506: 12481: 12457: 12422: 12398: 12373: 12349: 12324: 12295: 12270: 12246: 12237: 12221: 12171: 12144: 12120: 12083: 12055: 11959: 11932: 11867: 11832: 11808: 11773: 11754: 11706: 11679: 11655: 11628: 11604: 11579: 11557: 11501: 11474: 11447: 11414: 11322: 11289: 11270: 11219: 11176: 11133: 11125: 11084: 11057: 11038: 10982: 10957: 10933: 10898: 10856:

Thum T, Galuppo P, Wolf C, Fiedler J, Kneitz S, van Laake LW, et al. (July 2007).

10815:

Zhao Y, Ransom JF, Li A, Vedantham V, von Drehle M, Muth AN, et al. (April 2007).

10789: 10754: 10685: 10658: 10567:

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Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, et al. (November 2005).

8484: 8436: 8411: 8352: 8325: 8301: 8276: 8252: 8227: 8177:

Cock JM, Sterck L, Rouzé P, Scornet D, Allen AE, Amoutzias G, et al. (June 2010).

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Alles J, Fehlmann T, Fischer U, Backes C, Galata V, Minet M, et al. (April 2019).

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Võsa U, Vooder T, Kolde R, Fischer K, Välk K, Tõnisson N, et al. (October 2011).

9614: 9579: 8677: 8652: 6455: 6428: 6145: 6120: 5885: 5868: 5844: 5827: 4878:"Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex" 4853: 4828: 4629:"Characterization and identification of microRNA core promoters in four model species" 4604: 4579: 4347: 4322: 3935: 3918: 3160: 3143: 2549: 2524: 2497: 2472: 2366: 2076: 2059: 1793:

significantly inhibited adipogenesis and repressed induction of the master regulators

1673:

miRNAs can be either upregulated or downregulated in response to chronic alcohol use.

1425:

Pre-mRNA sequence of miR-712 is generated from the murine ribosomal RN45s gene at the

1156:

oligo or a 2'-O-methyl RNA oligo. A specific miRNA can be silenced by a complementary

889: 848:

The function of miRNAs appears to be in gene regulation. For that purpose, a miRNA is

703: 439:. Animal miRNAs are initially transcribed as part of one arm of an ~80 nucleotide RNA 283:. In this disorder, the miRNAs have a dual role working as both tumor suppressors and 177:'s team, including Wightman and Ha. These groups published back-to-back papers on the 125:

In cells of humans and other animals, miRNAs primarily act by destabilizing the mRNA.

15762: 15626: 15588: 15581: 15532: 15484: 15222: 15131: 13680: 13675: 13658: 13632: 13609: 13597: 13543: 13492: 13441: 13373: 13324: 13319: 13279: 13232: 13220: 13177: 13126: 13064: 13029: 13024: 13007: 12988: 12944: 12903: 12844: 12787: 12752: 12711: 12657: 12622: 12570: 12511: 12462: 12403: 12354: 12340: 12300: 12251: 12176: 12125: 12047: 12005: 11964: 11913: 11872: 11813: 11746: 11711: 11660: 11609: 11549: 11506: 11452: 11362: 11327: 11262: 11211: 11168: 11108: 11089: 11030: 10987: 10938: 10879: 10838: 10794: 10731: 10690: 10639: 10590: 10541: 10506: 10457: 10403: 10344: 10303: 10254: 10203: 10180: 10136: 10124: 10094: 10068: 10027: 9970: 9929: 9879: 9840:"MiR-205 and MiR-373 Are Associated with Aggressive Human Mucinous Colorectal Cancer" 9817: 9768: 9729: 9682: 9670: 9619: 9560: 9511: 9482:"Mutation altering the miR-184 seed region causes familial keratoconus with cataract" 9454: 9418: 9389:"miR2Disease: a manually curated database for microRNA deregulation in human disease" 9369: 9310: 9261: 9212: 9163: 9112: 9077: 9028: 8971: 8922: 8854: 8831: 8780: 8731: 8682: 8633: 8582: 8533: 8476: 8441: 8410:

Tjaden B, Goodwin SS, Opdyke JA, Guillier M, Fu DX, Gottesman S, et al. (2006).

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Ohman M (October 2007). "A-to-I editing challenger or ally to the microRNA process".

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Another role for miRNA in cancers is to use their expression level for prognosis. In

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that were involved in or affected the transcription of microRNAs from ChIP-seq data.

13644: 13248:"The Critical Role of miRNAs in Regulation of Flowering Time and Flower Development" 12669: 12060: 11223: 10553: 10080: 9466: 8983: 8116: 7983: 7824: 7781: 7635: 7267: 7250: 5042: 4461: 4079: 4036: 3975: 3597: 3090: 3039: 2983: 2927: 2274: 2231: 1196:

A mutation in the seed region of miR-96 causes hereditary progressive hearing loss.

15452: 14590: 14298: 14268: 13670: 13624: 13587: 13579: 13533: 13523: 13482: 13472: 13431: 13423: 13363: 13355: 13314: 13306: 13269: 13259: 13212: 13167: 13157: 13116: 13106: 13076: 13056: 13019: 12978: 12934: 12893: 12883: 12834: 12826: 12799: 12779: 12742: 12701: 12693: 12649: 12612: 12604: 12560: 12550: 12501: 12497: 12493: 12452: 12442: 12393: 12385: 12344: 12336: 12290: 12282: 12241: 12233: 12166: 12156: 12115: 12105: 12039: 11995: 11954: 11944: 11903: 11862: 11852: 11803: 11793: 11758: 11738: 11701: 11691: 11650: 11640: 11599: 11591: 11541: 11496: 11486: 11442: 11434: 11354: 11317: 11309: 11274: 11254: 11203: 11180: 11160: 11100: 11079: 11069: 11042: 11022: 10977: 10969: 10958:"Expression of microRNAs is dynamically regulated during cardiomyocyte hypertrophy" 10928: 10918: 10869: 10858:"MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure" 10828: 10784: 10774: 10721: 10680: 10670: 10629: 10621: 10580: 10533: 10496: 10488: 10447: 10439: 10393: 10383: 10334: 10293: 10285: 10244: 10236: 10198:

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cultured cells, shows that translational repression is caused by the disruption of

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AGO2 (grey) in complex with a microRNA (light blue) and its target mRNA (dark blue)

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