Non-coding RNA - Knowledge

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form one of two possible structures in regions encoding very short peptide sequences that are rich in the end product amino acid of the operon. A terminator structure forms when there is an excess of the regulatory amino acid and ribosome movement over the leader transcript is not impeded. When there

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The B2 RNA is a small noncoding RNA polymerase III transcript that represses mRNA transcription in response to heat shock in mouse cells. B2 RNA inhibits transcription by binding to core Pol II. Through this interaction, B2 RNA assembles into preinitiation complexes at the promoter and blocks RNA

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studies suggest that there are thousands of non-coding transcripts. Many of the newly identified ncRNAs have unknown functions, if any. There is no consensus on how much of non-coding transcription is functional: some believe most ncRNAs to be non-functional "junk RNA", spurious transcriptions,

1229:. A mouse model engineered to have a duplication of the SNORD115 cluster displays autistic-like behaviour. A recent small study of post-mortem brain tissue demonstrated altered expression of long non-coding RNAs in the prefrontal cortex and cerebellum of autistic brains as compared to controls. 1192:

tumor suppressor is arguably the most important agent in preventing tumor formation and progression. The p53 protein functions as a transcription factor with a crucial role in orchestrating the cellular stress response. In addition to its crucial role in cancer, p53 has been implicated in other

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Noncoding RNAs belong to several groups and are involved in many cellular processes. These range from ncRNAs of central importance that are conserved across all or most cellular life through to more transient ncRNAs specific to one or a few closely related species. The more conserved ncRNAs are

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Another example of non-coding RNA dysregulated in cancer cells is the long non-coding RNA Linc00707. Linc00707 is upregulated and sponges miRNAs in human bone marrow-derived mesenchymal stem cells, in hepatocellular carcinoma, gastric cancer or breast cancer, and thus promotes osteogenesis,

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and identification of the 5' and 3' ends then helped arrange the fragments to establish the RNA sequence. Of the three structures originally proposed for this tRNA, the 'cloverleaf' structure was independently proposed in several following publications. The cloverleaf

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regulate gene expression. A single miRNA can reduce the expression levels of hundreds of genes. The mechanism by which mature miRNA molecules act is through partial complementarity to one or more messenger RNA (mRNA) molecules, generally in

1213:. Prader–Willi is a developmental disorder associated with over-eating and learning difficulties. SNORD116 has potential target sites within a number of protein-coding genes, and could have a role in regulating alternative splicing. 757:

is a deficiency of the charged tRNA of the regulatory amino acid the ribosome translating the leader peptide stalls and the antiterminator structure forms. This allows RNA polymerase to transcribe the operon. Known RNA leaders are

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diseases including diabetes, cell death after ischemia, and various neurodegenerative diseases such as Huntington, Parkinson, and Alzheimer. Studies have suggested that p53 expression is subject to regulation by non-coding RNA.

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Xie M, Ma T, Xue J, Ma H, Sun M, Zhang Z, et al. (February 2019). "The long intergenic non-protein coding RNA 707 promotes proliferation and metastasis of gastric cancer by interacting with mRNA stabilizing protein HuR".

1127:. The miRNAs are involved in the large scale regulation of many protein coding genes, the Y RNAs are important for the initiation of DNA replication, telomerase RNA that serves as a primer for telomerase, an RNP that extends 969:, are RNAs that have two distinct functions. The majority of the known bifunctional RNAs are mRNAs that encode both a protein and ncRNAs. However, a growing number of ncRNAs fall into two different ncRNA categories; e.g., 1284:. BACE1-AS regulates the expression of BACE1 by increasing BACE1 mRNA stability and generating additional BACE1 through a post-transcriptional feed-forward mechanism. By the same mechanism it also raises concentrations of 4317:

Pibouin L, Villaudy J, Ferbus D, Muleris M, Prospéri MT, Remvikos Y, Goubin G (February 2002). "Cloning of the mRNA of overexpression in colon carcinoma-1: a sequence overexpressed in a subset of colon carcinomas".

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Bolton PF, Veltman MW, Weisblatt E, Holmes JR, Thomas NS, Youings SA, et al. (September 2004). "Chromosome 15q11-13 abnormalities and other medical conditions in individuals with autism spectrum disorders".

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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".

382:, is an evolutionary relative of RNase MRP. RNase P matures tRNA sequences by generating mature 5'-ends of tRNAs through cleaving the 5'-leader elements of precursor-tRNAs. Another ubiquitous RNP called 5256:

Ding F, Prints Y, Dhar MS, Johnson DK, Garnacho-Montero C, Nicholls RD, Francke U (June 2005). "Lack of Pwcr1/MBII-85 snoRNA is critical for neonatal lethality in Prader-Willi syndrome mouse models".

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Thind AS, Monga I, Thakur PK, Kumari P, Dindhoria K, Krzak M, et al. (November 2021). "Demystifying emerging bulk RNA-Seq applications: the application and utility of bioinformatic methodology".

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Kim SH, Quigley GJ, Suddath FL, McPherson A, Sneden D, Kim JJ, et al. (January 1973). "Three-dimensional structure of yeast phenylalanine transfer RNA: folding of the polynucleotide chain".

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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".

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contributes to hepatocellular carcinoma progression, promotes proliferation and metastasis, or indirectly regulates expression of proteins involved in cancer aggressiveness, respectively.

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Housman G, Ulitsky I (January 2016). "Methods for distinguishing between protein-coding and long noncoding RNAs and the elusive biological purpose of translation of long noncoding RNAs".

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Zhang J, King ML (December 1996). "Xenopus VegT RNA is localized to the vegetal cortex during oogenesis and encodes a novel T-box transcription factor involved in mesodermal patterning".

934:, is a negative regulator of Xist. X chromosomes lacking Tsix expression (and thus having high levels of Xist transcription) are inactivated more frequently than normal chromosomes. In 4074:"The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-alpha (ERalpha) and represses ERalpha messenger RNA and protein expression in breast cancer cell lines" 1384:. This eliminates the ambiguity when addressing a gene "encoding a non-coding" RNA. Besides, there may be a number of ncRNAs that are misannoted in published literature and datasets. 865:. The repeats are separated by spacers of similar length. It has been demonstrated that these spacers can be derived from phage and subsequently help protect the cell from infection. 2225:

Zachau HG, Dütting D, Feldmann H, Melchers F, Karau W (1966). "Serine specific transfer ribonucleic acids. XIV. Comparison of nucleotide sequences and secondary structure models".

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Fu X, Ravindranath L, Tran N, Petrovics G, Srivastava S (March 2006). "Regulation of apoptosis by a prostate-specific and prostate cancer-associated noncoding gene, PCGEM1".

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are nearly synonymous, however others have pointed out that a large proportion of annotated ncRNAs likely have no function. It also has been suggested to simply use the term

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Hirota K, Miyoshi T, Kugou K, Hoffman CS, Shibata T, Ohta K (November 2008). "Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs".

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represses translation by binding to Shine-Dalgarno sequences thereby occluding ribosome binding. OxyS RNA is induced in response to oxidative stress in Escherichia coli.

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Candeias MM, Malbert-Colas L, Powell DJ, Daskalogianni C, Maslon MM, Naski N, et al. (September 2008). "P53 mRNA controls p53 activity by managing Mdm2 functions".

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Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, et al. (December 2005). "The widespread impact of mammalian MicroRNAs on mRNA repression and evolution".

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Tu J, Zhao Z, Xu M, Chen M, Weng Q, Wang J, Ji J (July 2019). "LINC00707 contributes to hepatocellular carcinoma progression via sponging miR-206 to increase CDK14".

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Lerner MR, Boyle JA, Hardin JA, Steitz JA (January 1981). "Two novel classes of small ribonucleoproteins detected by antibodies associated with lupus erythematosus".

1288:, the main constituent of senile plaques. BACE1-AS concentrations are elevated in subjects with Alzheimer's disease and in amyloid precursor protein transgenic mice. 493:

Another group of introns can catalyse their own removal from host transcripts; these are called self-splicing RNAs. There are two main groups of self-splicing RNAs:

1361: 1245:, a disease associated with an array of symptoms such as short stature, sparse hair, skeletal abnormalities and a suppressed immune system that is frequent among 1447:

Cheng J, Kapranov P, Drenkow J, Dike S, Brubaker S, Patel S, et al. (May 2005). "Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution".

1352:) from ncRNA, to describe regions functional at the RNA level that may or may not be stand-alone RNA transcripts. This implies that fRNA (such as riboswitches, 5054:

Yuan RX, Bao D, Zhang Y (May 2020). "Linc00707 promotes cell proliferation, invasion, and migration via the miR-30c/CTHRC1 regulatory loop in breast cancer".

4829:"Long noncoding RNA LINC00707 sponges miR-370-3p to promote osteogenesis of human bone marrow-derived mesenchymal stem cells through upregulating WNT2B" 3255:

Espinoza CA, Allen TA, Hieb AR, Kugel JF, Goodrich JA (September 2004). "B2 RNA binds directly to RNA polymerase II to repress transcript synthesis".

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is restricted to eukaryotes. Both groups of ncRNA are involved in the maturation of rRNA. The snoRNAs guide covalent modifications of rRNA, tRNA and

1172:. Likewise, a screen of 17 miRNAs that have been predicted to regulate a number of breast cancer associated genes found variations in the microRNAs 326:. Proteins are shown in blue and the two RNA strands in orange and yellow. The small patch of green in the center of the subunit is the active site. 3349:

Park Y, Kelley RL, Oh H, Kuroda MI, Meller VH (November 2002). "Extent of chromatin spreading determined by roX RNA recruitment of MSL proteins".

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Ban N, Nissen P, Hansen J, Moore PB, Steitz TA (August 2000). "The complete atomic structure of the large ribosomal subunit at 2.4 A resolution".

2535: 5643:"Variability of clinical and laboratory features among patients with ribonuclease mitochondrial RNA processing endoribonuclease gene mutations" 450:

or tri-snRNP. There are two different forms of the spliceosome, the major and minor forms. The ncRNA components of the major spliceosome are

1333: 1161: 3704:"Potential structural role of non-coding and coding RNAs in the organization of the cytoskeleton at the vegetal cortex of Xenopus oocytes" 284: 2728: 2566:"Computational Identification of piRNAs Using Features Based on RNA Sequence, Structure, Thermodynamic and Physicochemical Properties" 4025:"Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and broad-Complex gene activity" 244:

was next to be discovered, followed by URNA in the early 1980s. Since then, the discovery of new non-coding RNAs has continued with

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Holley RW, Apgar J, Everett GA, Madison JT, Marquisee M, Merrill SH, et al. (March 1965). "Structure of a Ribonucleic Acid".

6492: 3402:"A dual function for a bacterial small RNA: SgrS performs base pairing-dependent regulation and encodes a functional polypeptide" 780: 3786:"Identification of conserved secondary structures and expansion segments in enod40 RNAs reveals new enod40 homologues in plants" 988:. However, a handful of other bifunctional RNAs are known to exist (e.g., steroid receptor activator/SRA, VegT RNA, Oskar RNA, 5684:"Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase" 5005:"MicroRNA-876 is sponged by long noncoding RNA LINC00707 and directly targets metadherin to inhibit breast cancer malignancy" 1659: 1423: 277: 700:

A recent study has shown that just the act of transcription of ncRNA sequence can have an influence on gene expression.

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Yarham JW, Elson JL, Blakely EL, McFarland R, Taylor RW (September 2010). "Mitochondrial tRNA mutations and disease".

6578: 4672:"Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia" 1916: 1165: 1041:

Non-coding RNAs are crucial in the development of several endocrine organs, as well as in endocrine diseases such as

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can promote the expression of certain miRNAs. Furthermore, this regulation occurs at distinct temporal points within

6865: 1173: 1146: 1142: 3612:"Steroid receptor RNA activator (SRA1): unusual bifaceted gene products with suspected relevance to breast cancer" 6870: 725: 615: 6326:"Non-coding RNA fragments account for the majority of annotated piRNAs expressed in somatic non-gonadal tissues" 712:. Chromatin is progressively converted to an open configuration, as several species of ncRNAs are transcribed. 1188:

mutations, lending the possibility that familial breast cancer may be caused by variation in these miRNAs. The

1157: 721: 2966:"Structural insights into RNA quality control: the Ro autoantigen binds misfolded RNAs via its central cavity" 6767: 6653: 1242: 1169: 1012:

There is an important link between certain non-coding RNAs and the control of hormone-regulated pathways. In

501:. These ncRNAs catalyze their own excision from mRNA, tRNA and rRNA precursors in a wide range of organisms. 487: 483: 375: 543:

protein (white) binds the end of a double-stranded Y RNA (red) and a single stranded RNA (blue). (PDB: 1YVP

1222: 1206: 1150: 794: 570: 509: 139: 5543:"Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia" 5392:

Cook EH, Scherer SW (October 2008). "Copy-number variations associated with neuropsychiatric conditions".

5099:"Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster" 1504:"Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project" 1049:

increased global transcription of the noncoding RNAs called lncRNAs near estrogen-activated coding genes.

6931: 6880: 6875: 6860: 6485: 6446: 6275:"Many lncRNAs, 5'UTRs, and pseudogenes are translated and some are likely to express functional proteins" 1132: 1116: 939: 638: 383: 5445:"Abnormal behavior in a chromosome-engineered mouse model for human 15q11-13 duplication seen in autism" 4227: 2715:

Poole A, Jeffares D, Penny D (October 1999). "Early evolution: prokaryotes, the new kids on the block".

2143: 3927:"Dual-function Spot 42 RNA encodes a 15-amino acid protein that regulates the CRP transcription factor" 562: 6114:

Pedersen JS, Bejerano G, Siepel A, Rosenbloom K, Lindblad-Toh K, Lander ES, et al. (April 2006).

2543: 791:. When iron concentration is low, IRPs bind the ferritin mRNA IRE leading to translation repression. 342:

are the 'factories' where translation takes place in the cell. The ribosome consists of more than 60%

2186: 1210: 1177: 951: 897: 892:. The telomeres contain condensed DNA material, giving stability to the chromosomes. The enzyme is a 709: 498: 354:. Ribosomal RNAs catalyse the translation of nucleotide sequences to protein. Another set of ncRNAs, 2164:

Madison JT, Everett GA, Kung H (July 1966). "Nucleotide sequence of a yeast tyrosine transfer RNA".

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Washietl S, Pedersen JS, Korbel JO, Stocsits C, Gruber AR, Hackermüller J, et al. (June 2007).

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Bazeley PS, Shepelev V, Talebizadeh Z, Butler MG, Fedorova L, Filatov V, Fedorov A (January 2008).

3067:"Dynamic interaction of Y RNAs with chromatin and initiation proteins during human DNA replication" 2780: 1091:, mutations or imbalances in the ncRNA repertoire within the body can cause a variety of diseases. 770: 494: 422:

Electron microscopy images of the yeast spliceosome. Note the bulk of the complex is in fact ncRNA.

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Ding F, Li HH, Zhang S, Solomon NM, Camper SA, Cohen P, Francke U (March 2008). Akbarian S (ed.).

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Ridanpää M, van Eenennaam H, Pelin K, Chadwick R, Johnson C, Yuan B, et al. (January 2001).

1499: 766: 758: 210: 6458:— a curated source of data related to over non-coding RNA databases available over the internet 4631:"A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia" 3569:

Ender C, Krek A, Friedländer MR, Beitzinger M, Weinmann L, Chen W, et al. (November 2008).

6900: 6593: 6478: 5301:"snoTARGET shows that human orphan snoRNA targets locate close to alternative splice junctions" 3743:

Jenny A, Hachet O, Závorszky P, Cyrklaff A, Weston MD, Johnston DS, et al. (August 2006).

2775: 2181: 1651: 1403: 1281: 802: 753: 331: 308:, and their current roles remain mostly in regulation of information flow from DNA to protein. 160: 51: 5146:

Skryabin BV, Gubar LV, Seeger B, Pfeiffer J, Handel S, Robeck T, et al. (December 2007).

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Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, et al. (October 2005).

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proteins. These piRNA complexes (piRCs) have been linked to transcriptional gene silencing of

6777: 6621: 6116:"Identification and classification of conserved RNA secondary structures in the human genome" 5682:

Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, et al. (July 2008).

5148:"Deletion of the MBII-85 snoRNA gene cluster in mice results in postnatal growth retardation" 1254: 893: 776: 762: 749: 387: 235: 5641:

Kavadas FD, Giliani S, Gu Y, Mazzolari E, Bates A, Pegoiani E, et al. (December 2008).

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Sahoo T, del Gaudio D, German JR, Shinawi M, Peters SU, Person RE, et al. (June 2008).

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Brosius J (May 2005). "Waste not, want not--transcript excess in multicellular eukaryotes".

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Lewis MA, Quint E, Glazier AM, Fuchs H, De Angelis MH, Langford C, et al. (May 2009).

5401: 5210: 5199:"SnoRNA Snord116 (Pwcr1/MBII-85) deletion causes growth deficiency and hyperphagia in mice" 4683: 4587: 4536: 4265: 4183: 3938: 3472: 3413: 3358: 3307: 3172: 2873: 2767: 2673: 2622: 2446: 2391: 2332: 2273: 2173: 2098: 2025: 2016:

Caspersson T, Schultz J (1939). "Pentose nucleotides in the cytoplasm of growing tissues".

1515: 1502:, Guigó R, Gingeras TR, Margulies EH, et al. (ENCODE Project Consortium) (June 2007). 1456: 817: 505: 305: 152: 4390:"GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer" 1648:

Non-coding RNAs and Epigenetic Regulation of Gene Expression: Drivers of Natural Selection

900:, which is used as a template when it elongates telomeres, which are shortened after each 8: 6807: 6790: 6648: 6531: 4480:"Noncoding human Y RNAs are overexpressed in tumours and required for cell proliferation" 1909:

RNA, The Epicenter of Genetic Information : A New Understanding of Molecular Biology

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sequences are found upstream of the first gene of amino acid biosynthetic operons. These

731: 642: 265: 231: 163:; he reasoned that RNA is better suited to base-pair with an mRNA transcript than a pure 17: 6131: 5965:

Zifa E, Giannouli S, Theotokis P, Stamatis C, Mamuris Z, Stathopoulos C (January 2007).

5405: 5214: 4687: 4591: 4540: 4269: 4187: 3942: 3476: 3417: 3362: 3311: 3208:"A role for the catalytic ribonucleoprotein RNase P in RNA polymerase III transcription" 3176: 3065:

Zhang AT, Langley AR, Christov CP, Kheir E, Shafee T, Gardiner TJ, Krude T (June 2011).

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Jones, Thomas A.; Otto, Wolfgang; Marz, Manja; Eddy, Sean R.; Stadler, Peter F. (2009).

2877: 2813:"Sequence analysis of RNase MRP RNA reveals its origination from eukaryotic RNase P RNA" 2771: 2677: 2626: 2450: 2395: 2336: 2277: 2177: 2102: 2029: 1519: 1460: 629:

is required for the normal and efficient transcription of various ncRNAs transcribed by

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Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. (November 2002).

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for more information). The direct function of the long mRNA-like ncRNAs is less clear.

1066: 946:(RNA on the X) RNAs are involved in dosage compensation. Both Xist and roX operate by 943: 679: 630: 148: 130:

while others expect that many non-coding transcripts have functions to be discovered.

107: 5559: 5542: 4706: 4671: 4446: 4331: 4172:"Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation" 4041: 4024: 4001: 2581: 2414: 2379: 2378:

Ladner JE, Jack A, Robertus JD, Brown RS, Rhodes D, Clark BF, Klug A (November 1975).

2355: 2320: 2296: 2261: 1934:"Long Noncoding RNAs and Repetitive Elements: Junk or Intimate Evolutionary Partners?" 1324:

A number of mutations within mitochondrial tRNAs have been linked to diseases such as

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genes. RNase P exerts its role in transcription through association with Pol III and

544: 221:) and then with takadiastase ribonuclease Tl (producing fragments which finished with 62:

sequence from which a functional non-coding RNA is transcribed is often called an RNA

6785: 6747: 6740: 6691: 6643: 6390: 6355: 6306: 6255: 6206: 6155: 6096: 6091: 6067:"A computational approach to identify genes for functional RNAs in genomic sequences" 6066: 6047: 5988: 5939: 5904: 5855: 5806: 5749: 5713: 5664: 5623: 5574: 5523: 5474: 5417: 5366: 5362: 5330: 5273: 5238: 5179: 5128: 5083: 5071: 5036: 4977: 4922: 4895: 4860: 4801: 4760: 4711: 4652: 4603: 4552: 4509: 4460: 4411: 4388:

Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT (January 2009).

4370: 4335: 4303: 4291: 4209: 4152: 4095: 4046: 4005: 3966: 3907: 3850: 3815: 3766: 3725: 3676: 3641: 3592: 3551: 3500: 3441: 3374: 3323: 3272: 3237: 3188: 3137: 3096: 3047: 2995: 2946: 2938: 2891: 2842: 2793: 2732: 2689: 2638: 2595: 2508: 2462: 2419: 2360: 2301: 2242: 2199: 2114: 2068: 1998: 1967: 1955: 1912: 1889: 1835: 1797: 1762: 1711: 1655: 1625: 1576: 1541: 1472: 1393: 1042: 806: 701: 664: 661: 335: 99: 31: 6000: 5951: 5777:"An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice" 5761: 5586: 5378: 5285: 4989: 4907: 4813: 4058: 3688: 3386: 3284: 3149: 2903: 2744: 2701: 2520: 2474: 2126: 1780:

Hüttenhofer A, Schattner P, Polacek N (May 2005). "Non-coding RNAs: hope or hype?".

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Nakatani J, Tamada K, Hatanaka F, Ise S, Ohta H, Inoue K, et al. (June 2009).

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specificity factor. This interaction represses expression from a sigma70-dependent

634: 297: 191: 187: 6241: 3018:"Functional requirement of noncoding Y RNAs for human chromosomal DNA replication" 2110: 601:, transcribed from the enhancer region of a gene, act to promote gene expression. 190:, its structure was published in 1965. To produce a purified alanine tRNA sample, 121:

The number of non-coding RNAs within the human genome is unknown; however, recent

6735: 6706: 6386: 6140: 5223: 5164: 5067: 4973: 3587: 3570: 3536: 3485: 2789: 2458: 2195: 1747: 1297: 844: 836: 788: 582: 554: 513: 395: 122: 6465: 6441: 2862:"The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C" 2238: 1994: 6827: 6730: 5659: 5642: 5460: 5316: 4676: