Jump to content

Non-coding RNA

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by Ppgardne (talk | contribs) at 11:24, 16 February 2009 (Added a section on bifunctional RNAs.). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. Less-frequently used synonyms are non-protein-coding RNA (npcRNA), non-messenger RNA (nmRNA), small non-messenger RNA (snmRNA), functional RNA (fRNA). The term small RNA (sRNA) is often used for bacteria. The DNA sequence from which a non-coding RNA is transcribed as the end product is often called an RNA gene or non-coding RNA gene.

Non-coding RNA genes include highly abundant and functionally important RNAs such as transfer RNA (tRNA) and ribosomal RNA (rRNA), as well as RNAs such as snoRNAs, microRNAs, siRNAs and piRNAs and lastly long ncRNAs that include examples such as Xist and HOTAIR (see here for a more complete list of ncRNAs). The number of ncRNAs encoded within the human genome is unknown, however recent transcriptomic and bioinformatic studies suggest the existence of thousands of ncRNAs.[1][2][3] Since most of the newly identified ncRNAs have not been validated for their function, it is possible that many are non-functional.[4]

Biological roles of ncRNA

Noncoding RNAs are a diverse group of genes 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 thought to be molecular fossils or relics from LUCA and the RNA world.[5][6][7]

ncRNAs in translation

An illustration of the central dogma of molecular biology annotated with the processes ncRNAs are invloved in. RNPs are shown in red, ncRNAs are shown in blue.

Many of the very well conserved, essential and abundant ncRNAs are involved in translation. Ribonucleoprotein (RNP) particles called ribosomes are the 'factories' where translation takes place in the cell. The ribosome consists of more than 60% ribosomal RNA, these are made up of 3 ncRNAs in prokaryotes and 4 ncRNAs in eukaryotes. Ribosomal RNAs catalyse the translation of nucleotide sequences to protein. Another set of ncRNAs, Transfer RNAs, form an 'adaptor molecule' between mRNA and protein. The H/ACA box and C/D box snoRNAs are ncRNAs found in archaea and eukaryotes, RNase MRP is restricted to eukaryotes, both groups of ncRNA are involved in the maturation of rRNA. The snoRNAs guide covalent modifications of rRNA, tRNA and snRNAs, RNase MRP cleaves the internal transcribed spacer 1 between 18S and 5.8S rRNAs. The ubiquitous ncRNA, RNase P, is an evolutionary relative of RNase MRP.[8] 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 SRP recognizes and transports specific nascent proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes. In bacteria Transfer-messenger RNA (tmRNA) is an RNP is involved in rescuing stalled ribosomes, tagging incomplete polypeptides and promoting the degradation of aberrant mRNA.

ncRNAs in RNA splicing

In eukaryotes the spliceosome performs the splicing reactions essential for removing intron sequences, this process is required for the formation of mature mRNA. The spliceosome is another RNP often also known as the snRNP or tri-snRNP. There are two different forms of the spliceosome, the major and minor forms. The ncRNA components of the major spliceosome are U1, U2, U4 and U5. The ncRNA components of the minor spliceosome are U11, U12, U5, U4atac and U6atac.

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, these are the group I catalytic intron and group II catalytic intron. These ncRNAs catalyze their own excision from mRNA, tRNA and rRNA precursors in a wide range of organisms.

In mammals it has been found that snoRNAs can also regulate the alternative splicing of mRNA, for example snoRNA HBII-52 regulates the splicing of serotonin receptor 2C.[9]

In nematodes the SmY ncRNA appears to be involved in mRNA trans-splicing.

ncRNAs in gene regulation

The expression of many thousands of genes are regulated by ncRNAs. This regulation can occur in trans or in cis.

trans-acting ncRNAs

In higher eukaryotes MicroRNAs 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 complementary to one or more messenger RNA (mRNA) molecules, generally in 3' UTRs. The main function of miRNAs is to down-regulate gene expression.

The ncRNA RNase P has also been shown to influence gene expression. In the human nucleus RNase P is required for the normal and efficient transcription of various ncRNAs transcribed by RNA polymerase III. These include tRNA, 5S rRNA, SRP RNA and U6 snRNA genes. RNase P exerts its role in transcription through association with Pol III and chromatin of active tRNA and 5S rRNA genes. [10]

It has been shown that 7SK RNA, a metazoan ncRNA, acts as a negative regulator of the RNA polymerase II elongation factor P-TEFb, and that this activity is influenced by stress response pathways.

The bacterial ncRNA, 6S RNA, specifically associates with RNA polymerase holoenzyme containing the sigma70 specificity factor. This interaction represses expression from a sigma70-dependent promoter during stationary phase.

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

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 synthesis. [11]

A recent study has shown that just the act of transcription of ncRNA sequence can have an influence on gene expression. RNA polymerase II transcription of ncRNAs is required for chromatin remodelling in the Schizosaccharomyces pombe. Chromatin is progressively converted to an open configuration, as several species of ncRNAs are transcribed. [12]

cis-acting ncRNAs

Main articles: Five prime untranslated region and Three prime untranslated region

A number of ncRNAs are embedded in the 5' UTRs of protein coding genes and influence their expression in various ways. For example, a riboswitch can directly bind a small target molecule, the binding of the target affects the gene's activity.

RNA leader sequences are found upstream of of the first gene of in amino acid biosynthetic operons. These RNA elements 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 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 Histidine operon leader, Leucine operon leader, Threonine operon leader and the Tryptophan operon leader.

Iron response elements (IRE) are bound by iron response proteins (IRP). The IRE is found in UTRs (Untranslated Regions) of various mRNAs whose products are involved in iron metabolism. When iron concentration is low, IRPs bind the ferritin mRNA IRE leading to translation repression.

Internal ribosome entry sites (IRES) are a RNA structure that allow for translation initiation in the middle of a mRNA sequence as part of the process of protein synthesis.

ncRNAs and Genome defense

Piwi-interacting RNAs (piRNAs) expressed in mammalian testes and somatic cells, they form RNA-protein complexes with Piwi proteins. These piRNA complexes (piRCs) have been linked to transcriptional gene silencing of retrotransposons and other genetic elements in germ line cells, particularly those in spermatogenesis.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are repeats found in the DNA of many bacteria and archaea. 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.

ncRNAs and chromosome structure

Telomerase is an RNP enzyme that adds specific DNA sequence repeats ("TTAGGG" in vertebrates) to telomeric regions, which are found at the ends of eukaryotic chromosomes. The telomeres contain condensed DNA material, giving stability to the chromosomes. The enzyme is a reverse transcriptase that carries Telomerase RNA, which is used as a template when it elongates telomeres, which are shortened after each replication cycle.

Xist (X-inactive-specific transcript) is an long ncRNA gene on the X chromosome of the placental mammals that acts as major effector of the X chromosome inactivation process forming Barr bodies. An antisense RNA, Tsix, 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 drosophilids, which also use an XY sex-determination system, the roX (RNA on the X) RNAs are involved in dosage compensation. [13] Both Xist and roX operate by epigenetic regulation of transcription through the recruitment of histone-modifying enzymes.

bifunctional RNA

Bifunctional RNAs are RNAs that have two distinct functions, these are also known as dual function RNAs.[14][15] The majority of the known bifunctional RNAs are both mRNAs that encode a protein and ncRNAs. However there are also a growing number of ncRNAs that fall into two different ncRNA catagories eg. H/ACA box snoRNA and miRNA.[16][17]

Two well known examples of bifunctional RNAs are SgrS RNA and RNAIII. However, many other potential bifunctional RNAs such as SRA (Steroid Receptor Activator)[18], VegT RNA[19][20], Oskar RNA[21] and enod40[22].

ncRNAs and disease

As with proteins, mutations or imbalances in the ncRNA repertoire within the body can cause a variety of diseases.

ncRNAs and cancer

Many ncRNAs show abnormal expression patterns in cancerous tissues. These include miRNAs,[23] long mRNA-like ncRNAs[24][25], Telomerase RNA and Y RNAs.[26] The miRNAs are involved in the large scale regulation of many protein coding genes,[27][28] the Y RNAs are important for the initiation of DNA replication[29], telomerase RNA that serves as a primer for telomerase, an RNP that extends telomeric regions at chromosome ends (see telomeres and disease for more information). The direct function of the long mRNA-like ncRNAs is less clear.

ncRNAs and Prader-Willi syndrome

The deletion of the 48 copies of the C/D box snoRNA SNORD116 has been shown to be the primary cause of Prader-Willi syndrome.[30][31][32] Prader-Willi is a developmental disorder associated with over-eating and learning difficulties. The targets of SNORD116 are unknown, however a bioinformatic screen located 23 possible targets within protein coding genes, of these a large fraction were found to be alternatively spliced, suggesting a role of SNORD116 in the regulation of alternative splicing.[33]

ncRNAs and Alzheimer's disease

The antisense RNA, BACE1-AS is transcribed from the opposite strand to BACE1 and is upregulated in patients with Alzheimer's disease. [34] BACE1-AS regulates the expression of BACE1 by increasing BACE1 mRNA stability and generating additional BACE1 through a post-transcriptional feed-forward mechanism. BACE1-AS concentrations are elevated in subjects with Alzheimer's disease and in amyloid precursor protein transgenic mice. Showing that BACE1 mRNA expression is under the control of a regulatory noncoding RNA that may drive Alzheimer's disease–associated pathophysiology.

Distinction between functional RNA (fRNA) and ncRNA

The term ncRNA has been used, in addition to its above definition, to describe regions of mRNA that are functional at the RNA level, i.e. they have a biological function other than coding for protein even though they are on a protein-coding mRNA, for example riboswitches and the SECIS element. Indeed, there may be a significant overlap between ncRNA and protein-coding RNA regions[35] and are thus dual-functional: at the RNA level and at the protein level (e.g. SgrS RNA and RNAIII). However, these conflict with the strict Sequence Ontology's definition of ncRNA, which requires that a RNA does not contain any protein-coding sequence in order to be labeled ncRNA.

Several publications[36][37][38] have started using the term functional RNA (fRNA), as opposed to ncRNA, to describe regions functional at the RNA level that may or may not be stand-alone RNA transcripts. Therefore, every ncRNA is a fRNA, but there exist fRNA (such as riboswitches, SECIS elements, and other cis-regulatory regions) that are not ncRNA. Yet the term fRNA could also include mRNA as this is RNA coding for protein and hence is functional. Additionally artificially evolved RNAs also fall under the fRNA umbrella term. Some publications[39] state that the terms ncRNA and fRNA are nearly synonymous.

See also

References

  1. ^ Cheng J, Kapranov P, Drenkow J, Dike S, Brubaker S, Patel S, Long J, Stern D, Tammana H, Helt G, Sementchenko V, Piccolboni A, Bekiranov S, Bailey DK, Ganesh M, Ghosh S, Bell I, Gerhard DS, Gingeras TR (2005). "Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution". Science. 308 (5725): 1149–54. PMID 15790807.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ ENCODE Project Consortium (2007). "Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project". Nature. 447 (7146): 799–816. PMID 17571346.
  3. ^ Washietl S, Pedersen JS, Korbel JO, Stocsits C, Gruber AR, Hackermüller J, Hertel J, Lindemeyer M, Reiche K, Tanzer A, Ucla C, Wyss C, Antonarakis SE, Denoeud F, Lagarde J, Drenkow J, Kapranov P, Gingeras TR, Guigó R, Snyder M, Gerstein MB, Reymond A, Hofacker IL, Stadler PF (2007). "Structured RNAs in the ENCODE selected regions of the human genome". Genome Res. 17 (6): 852–64. PMID 17568003.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Hüttenhofer A, Schattner P, Polacek N (2005). "Non-coding RNAs: hope or hype?". Trends Genet. 21 (5): 289–97. PMID 15851066.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Jeffares DC, Poole AM, Penny D (1998). "Relics from the RNA world". J Mol Evol. 46 (1): 18–36. PMID 9419222.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ Poole AM, Jeffares DC, Penny D (1998). "The path from the RNA world". J Mol Evol. 46 (1): 1–17. PMID 9419221.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Poole A, Jeffares D, Penny D (1999). "Early evolution: prokaryotes, the new kids on the block". Bioessays. 21 (10): 880–9. PMID 10497339.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Zhu Y, Stribinskis V, Ramos KS, Li Y (2006). "Sequence analysis of RNase MRP RNA reveals its origination from eukaryotic RNase P RNA". RNA. 12 (5): 699–706. PMID 16540690.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ Kishore S, Stamm S (2006). "The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C". Science. 311 (5758): 230–231. doi:10.1126/science.1118265. PMID 16357227. {{cite journal}}: line feed character in |title= at position 67 (help)
  10. ^ Reiner R, Ben-Asouli Y, Krilovetzky I, Jarrous N (2006). "A role for the catalytic ribonucleoprotein RNase P in RNA polymerase III transcription". Genes Dev. 20 (12): 1621–35. PMID 16778078.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ Espinoza CA, Allen TA, Hieb AR, Kugel JF, Goodrich JA (2004). "B2 RNA binds directly to RNA polymerase II to repress transcript synthesis". Nat Struct Mol Biol. 11 (9): 822–9. PMID 15300239.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ Hirota K, Miyoshi T, Kugou K, Hoffman CS, Shibata T, Ohta K (2008). "Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs". Nature. 456 (7218): 130–4. PMID 18820678.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ Park Y, Kelley RL, Oh H, Kuroda MI, Meller VH (2002). "Extent of chromatin spreading determined by roX RNA recruitment of MSL proteins". Science. 298 (5598): 1620–3. PMID 12446910.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ Wadler CS, Vanderpool CK (2007). "A dual function for a bacterial small RNA: SgrS performs base pairing-dependent regulation and encodes a functional polypeptide". Proc Natl Acad Sci U S A. 104 (51): 20454–9. PMID 18042713.
  15. ^ Dinger ME, Pang KC, Mercer TR, Mattick JS (2008). "Differentiating protein-coding and noncoding RNA: challenges and ambiguities". PLoS Comput Biol. 4 (11): e1000176. PMID 19043537.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ Saraiya AA, Wang CC (2008). "snoRNA, a novel precursor of microRNA in Giardia lamblia". PLoS Pathog. 4 (11): e1000224. PMID 19043559.
  17. ^ Ender C, Krek A, Friedländer MR, Beitzinger M, Weinmann L, Chen W, Pfeffer S, Rajewsky N, Meister G (2008). "A human snoRNA with microRNA-like functions". Mol Cell. 32 (4): 519–28. PMID 19026782.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  18. ^ Leygue E (2007). "Steroid receptor RNA activator (SRA1): unusual bifaceted gene products with suspected relevance to breast cancer". Nucl Recept Signal. 5: e006. PMID 17710122.
  19. ^ Zhang J, King ML (1996). "Xenopus VegT RNA is localized to the vegetal cortex during oogenesis and encodes a novel T-box transcription factor involved in mesodermal patterning". Development. 122 (12): 4119–29. PMID 9012531.
  20. ^ Kloc M, Wilk K, Vargas D, Shirato Y, Bilinski S, Etkin LD (2005). "Potential structural role of non-coding and coding RNAs in the organization of the cytoskeleton at the vegetal cortex of Xenopus oocytes". Development. 132 (15): 3445–57. PMID 16000384.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  21. ^ Jenny A, Hachet O, Závorszky P, Cyrklaff A, Weston MD, Johnston DS, Erdélyi M, Ephrussi A (2006). "A translation-independent role of oskar RNA in early Drosophila oogenesis". Development. 133 (15): 2827–33. PMID 16835436.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ Gultyaev AP, Roussis A (2007). "Identification of conserved secondary structures and expansion segments in enod40 RNAs reveals new enod40 homologues in plants". Nucleic Acids Res. 35 (9): 3144–52. PMID 17452360.
  23. ^ Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005). "MicroRNA expression profiles classify human cancers". Nature. 435 (7043): 834–8. PMID 15944708.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  24. ^ Pibouin L, Villaudy J, Ferbus D, Muleris M, Prospéri MT, Remvikos Y, Goubin G (2002). "Cloning of the mRNA of overexpression in colon carcinoma-1: a sequence overexpressed in a subset of colon carcinomas". Cancer Genet Cytogenet. 133 (1): 55–60. PMID 11890990.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  25. ^ Fu X, Ravindranath L, Tran N, Petrovics G, Srivastava S (2006). "Regulation of apoptosis by a prostate-specific and prostate cancer-associated noncoding gene, PCGEM1". DNA Cell Biol. 25 (3): 135–41. PMID 16569192.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  26. ^ Christov CP, Trivier E, Krude T (2008). "Noncoding human Y RNAs are overexpressed in tumours and required for cell proliferation". Br J Cancer. 98 (5): 981–8. PMID 18283318.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  27. ^ Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, Burge CB, Bartel DP (2005). "The widespread impact of mammalian MicroRNAs on mRNA repression and evolution". Science. 310 (5755): 1817–21. PMID 16308420.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  28. ^ Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM (2005). "Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs". Nature. 433 (7027): 769–73. PMID 15685193.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  29. ^ Christov CP, Gardiner TJ, Szüts D, Krude T (2006). "Functional requirement of noncoding Y RNAs for human chromosomal DNA replication". Mol Cell Biol. 26 (18): 6993–7004. PMID 16943439.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  30. ^ Sahoo T, del Gaudio D, German JR, Shinawi M, Peters SU, Person RE, Garnica A, Cheung SW, Beaudet AL (2008). "Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster". Nat Genet. 40 (6): 719–21. PMID 18500341. {{cite journal}}: line feed character in |author= at position 63 (help); line feed character in |title= at position 23 (help)CS1 maint: multiple names: authors list (link)
  31. ^ {{cite journal |author=Ding F, Li HH, Zhang S, Solomon NM, Camper SA, Cohen P, Francke U |title=SnoRNA Snord116 (Pwcr1/MBII-85) deletion causes growth deficiency and hyperphagia in mice. |journal=PLoS ONE |volume=3 |issue=3 |pages=e1709 |year=2008 |pmid=18320030}}
  32. ^ Ding F, Prints Y, Dhar MS, Johnson DK, Garnacho-Montero C, Nicholls RD, Francke U (2005). "Lack of Pwcr1/MBII-85 snoRNA is critical for neonatal lethality in Prader-Willi syndrome mouse models". Mamm Genome. 16 (6): 424–31. PMID 16075369. {{cite journal}}: line feed character in |author= at position 27 (help); line feed character in |title= at position 8 (help)CS1 maint: multiple names: authors list (link)
  33. ^ Bazeley PS, Shepelev V, Talebizadeh Z, Butler MG, Fedorova L, Filatov V, Fedorov A (2008). "snoTARGET shows that human orphan snoRNA targets locate close to alternative splice junctions". Gene. 408 (1–2): 172–9. PMID 18160232.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  34. ^ Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, St Laurent G, Kenny PJ, Wahlestedt C (2008). "Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase". Nat Med. 14 (7): 723–30. PMID 18587408.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  35. ^ Marcel E. Dinger, Ken C. Pang, Tim R. Mercer, John S. Mattick (2008). "Differentiating Protein-Coding and Noncoding RNA: Challenges and Ambiguities". PLOS Computational Biology. 4 (11): e1000176.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  36. ^ Richard J. Carter, Inna Dubchak, Stephen R. Holbrook (2001). "A computational approach to identify genes for functional RNAs in genomic sequences". Nucleic Acids Research. 29 (19): 3928–3938.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  37. ^ Jakob Skou Pedersen, Gill Bejerano, Adam Siepel, Kate Rosenbloom, Kerstin Lindblad-Toh, Eric S. Lander, Jim Kent, Webb Miller, David Haussler (2006). "Identification and Classification of Conserved RNA Secondary Structures in the Human Genome". PLOS Computational Biology. 2 (4): e33. doi:10.1371/journal.pcbi.0020033.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  38. ^ Tomas Babak, Benjamin J Blencowe, Timothy R Hughes (2007). "Considerations in the identification of functional RNA structural elements in genomic alignments". BMC Bioinformatics. 8 (8): 33. doi:10.1186/1471-2105-8-21.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  39. ^ Sean Eddy (2001). "Non–coding RNA genes and the modern RNA world". Nature Reviews Genetics. 2 (2): 919–929. doi:10.1038/35103511.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Non-coding_RNA&oldid=271097015"