MicroRNA
156964
225422945
2008-07-13T16:43:53Z
Adeez
3919602
[[Image:Microrna secondary structure.png|thumb|right|The [[stem-loop]] [[secondary structure]] of a pre-microRNA from ''[[Brassica oleracea]]''.]]
In [[genetics]], '''microRNAs''' ('''miRNA''') are single-stranded [[RNA]] molecules of about 21–23 [[nucleotide]]s in length, which regulate [[gene expression]]. miRNAs are encoded by genes that are [[transcription (genetics)|transcribed]] from [[DNA]] but not [[translation (genetics)|translated]] into [[protein]] ([[non-coding RNA]]); instead they are processed from [[primary transcript]]s known as ''pri-miRNA'' to short [[stem-loop]] structures called ''pre-miRNA'' and finally to functional miRNA. Mature miRNA molecules are [[complementarity (molecular biology)| partially complementary]] to one or more [[messenger RNA]] (mRNA) molecules, and their main function is to downregulate gene expression.
They were first described in 1993 by Lee and colleagues in the Victor Ambros lab <ref name="miRNA discovery">{{cite journal | author=Lee RC, Feinbaum RL, Ambros V | year=1993| title=The C. elegans heterochronic gene [[Lin-4 microRNA precursor|lin-4]] encodes small RNAs with antisense complementarity to lin-14. |journal=Cell |volume=75 |pages=843–854| pmid=8252621| doi=10.1016/0092-8674(93)90529-Y}} </ref>, yet the term ''microRNA'' was only introduced in 2001 in a set of three articles in [[Science (journal)|Science]] ([[26 October]] [[2001]]).<ref>{{cite journal
|url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11679654
|title=Molecular biology. Glimpses of a tiny RNA world. |last=Ruvkun |first= G. |journal=Science |year=2001 |month=Oct 26
|volume=294 |issue=5543 |pages=797–9 |pmid=11679654
|doi=10.1126/science.1066315}}</ref> As of early 2008, computational analysis by [[IBM]] suggested the existence of as many as 50,000 different miRNAs in the typical mammalian cell, each with perhaps a thousand or more potential targets.<ref name="2008-Glaser"/>
==Formation and processing==
[[Image:MiRNA_processing.JPG|thumb|250px|MicroRNA (miRNA) is produced from precursor microRNA (pre-miRNA), which in turn is formed from a microRNA primary transcript (pri-miRNA).]]
The genes encoding miRNAs are much longer than the processed mature miRNA molecule; miRNAs are first transcribed as [[primary transcript]]s or pri-miRNA with a cap and poly-A tail and processed to short, 70-nucleotide [[stem-loop]] structures known as pre-miRNA in the [[cell nucleus]]. This processing is performed in animals by a [[protein complex]] known as the Microprocessor complex, consisting of the [[nuclease]] [[Drosha]] and the double-stranded RNA binding protein [[Pasha (protein)|Pasha]].<ref name="Denli">Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. (2004). ''Nature'' 432(7014):231-5.</ref> These pre-miRNAs are then processed to mature miRNAs in the [[cytoplasm]] by interaction with the [[endonuclease]] [[Dicer]], which also initiates the formation of the [[RNA-induced silencing complex]] (RISC).<ref name="Bernstein">Bernstein E, Caudy AA, Hammond SM, Hannon GJ. (2001). Role for a bidentate ribonuclease in the initiation step of RNA interference. ''Nature'' 409(6818):363-6.</ref> This complex is responsible for the gene silencing observed due to miRNA expression and [[RNA interference]]. The pathway in plants varies slightly due to their lack of [[Drosha]] homologs; instead, Dicer homologs alone effect several processing steps.<ref name="Kurihara">Kurihara Y, Watanabe Y. (2004). Arabidopsis micro-RNA biogenesis through Dicer-like 1 protein functions. ''Proc Natl Acad Sci USA'' 101(34):12753-8.</ref> The pathway is also different for miRNAs derived from [[intron]]ic stem-loops; these are processed by Dicer but not by Drosha.<ref>{{cite journal | title=Posttranscriptional control of neuronal development by microRNA networks | author=Gao F-B| journal=Trends in Neurosciences | year=2007| doi=10.1016/j.tins.2007.10.004 | volume=31 | pages=20}}</ref> Either the [[Sense (molecular biology)|sense strand]] or [[Sense (molecular biology)|antisense]] strand of DNA can function as templates to give rise to miRNA.<ref>{{cite journal |author=Stark A, Bushati N, Jan CH, ''et al'' |title=A single Hox locus in Drosophila produces functional microRNAs from opposite DNA strands |journal=Genes Dev. |volume=22 |issue=1 |pages=8–13 |year=2008 |pmid=18172160 |doi=10.1101/gad.1613108}}</ref>
Efficient processing of pre-miRNA by Drosha requires the presence of extended single-stranded RNA on both 3'- and 5'-ends of hairpin molecule.<ref>{{cite journal | author=Zeng Y, Cullen BR| title=Efficient processing of primary microRNA hairpins by Drosha requires flanking nonstructured RNA sequences| journal=J. Biol. Chem.| year=2005| volume=280| issue=30| pages=27595–603| url=http://www.jbc.org/cgi/content/full/280/30/27595 | doi=10.1074/jbc.M504714200| pmid=15932881}}</ref> These ssRNA motifs could be of different composition while their length is of high importance if processing is to take place at all. A bioinformatics analysis of human and fly pri-miRNAs revealed very similar structural regions, called 'basal segments', 'lower stems', 'upper stems' and 'terminal loops'; based on these conserved structures, thermodynamic profiles of pri-miRNA have been determined.<ref name="Han_2006">{{cite journal | author=Han J, Lee Y, Yeom K-H, Nam J-W, Heo I, Rhee J-K, Sohn SY, Cho Y, Zhang B-T, Kim VN| title=Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex| journal=Cell| year=2006| volume=125| issue=5| pages=887–901| url=http://www.cell.com/content/article/abstract?uid=PIIS0092867406005162 | doi=10.1016/j.cell.2006.03.043}}</ref> The Drosha complex cleaves RNA molecule ~2 helical turns away from the terminal loop and ~1 turn away from basal segments. In most analysed molecules this region contains unpaired nucleotides and the free energy of the duplex is relatively high compared to lower and upper stem regions{{Fact|date=October 2007}}. Most pre-miRNAs don't have a perfect double-stranded RNA (dsRNA) structure topped by a terminal loop. There are few possible explanations for such selectivity. One could be that dsRNAs longer than 21 base pairs activate interferon response and anti-viral machinery in the cell. Another plausible explanation could be that the thermodynamic profile of pre-miRNA determines which strand will be incorporated into Dicer complex. Indeed, clear similarities between pri-miRNAs encoded in respective (5'- or 3'-) strands have been demonstrated.<ref name="Han_2006"/>
When Dicer cleaves the pre-miRNA stem-loop, two complementary short RNA molecules are formed, but only one is integrated into the RISC complex. This strand is known as the ''guide strand'' and is selected by the [[argonaute]] protein, the catalytically active [[RNase]] in the RISC complex, on the basis of the stability of the [[5' end]].<ref name="Preall">Preall JB, He Z, Gorra JM, Sontheimer EJ. (2006). Short interfering RNA strand selection is independent of dsRNA processing polarity during RNAi in Drosophila. ''Curr Biol'' 16(5):530-5.</ref> The remaining strand, known as the ''anti-guide'' or ''passenger strand'', is degraded as a RISC complex substrate.<ref name="Gregory">Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. (2005). Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. ''Cell'' 123(4):631-40.</ref> After integration into the active RISC complex, miRNAs base pair with their complementary mRNA molecules and induce mRNA degradation by [[argonaute]] proteins, the catalytically active members of the RISC complex. It is as yet unclear how the activated RISC complex locates the mRNA targets in the cell, though it has been shown that the process is not coupled to ongoing protein translation from the mRNA.<ref name="Sen">Sen GL, Wehrman TS, Blau HM. (2005). mRNA translation is not a prerequisite for small interfering RNA-mediated mRNAs cleavage. ''Differentiation'' 73(6):287-93. </ref>
==Cellular functions==
The function of miRNAs appears to be in gene regulation. For that purpose, a miRNA is [[complementarity (molecular biology)|complementary]] to a part of one or more [[messenger RNA]]s (mRNAs). Animal miRNAs are usually complementary to a site in the [[3' UTR]] whereas plant miRNAs are usually complementary to coding regions of mRNAs. The [[Annealing (biology)|annealing]] of the miRNA to the mRNA then inhibits protein translation, but sometimes facilitates cleavage of the mRNA. This is thought to be the primary mode of action of plant miRNAs. In such cases, the formation of the double-stranded RNA through the binding of the miRNA triggers the degradation of the mRNA transcript through a process similar to [[RNA interference]] (RNAi), though in other cases it is believed that the miRNA complex blocks the protein translation machinery or otherwise prevents protein translation without causing the mRNA to be degraded. miRNAs may also target [[methylation]] of genomic sites which correspond to targeted mRNAs. miRNAs function in association with a complement of proteins collectively termed the miRNP.
This effect was first described for the worm ''[[C. elegans]]'' in [[1993]] by [[Victor Ambros]] and coworkers.<ref name="miRNA discovery"/> As of 2002, miRNAs have been confirmed in various [[plant]]s and [[animal]]s, including ''C. elegans'', [[human]] and the plant ''[[Arabidopsis thaliana]]''. Work at the [[University of Louisville]] has resulted in the production of [[DNA microarray|microarray]]s containing all known (at the time of production) miRNAs for human, mouse, rat, dog, ''C. elegans'' and ''[[Drosophila melanogaster|Drosophila]]'' species, tools referred to as '''MMChips'''<!-- redirect points to this section -->.<ref name="2008-Glaser"/> [[Agilent]] has subsequently commercialized a human miRNA microarray.<ref>
{{cite news | author=staff | title=miRNA Detection Technology | url= | format=print | work=Genetic Engineering & Biotechnology News
| publisher=Mary Ann Liebert, Inc. | page=30 | date=2007-06-15 | accessdate=2008-07-07
}}</ref>
Genes have been found in [[bacterium|bacteria]] that are similar to eukaryotic miRNA genes in the sense that they control mRNA abundance or translation by binding an mRNA by base pairing, however they are not generally considered to be miRNAs because the Dicer enzyme is not involved.
In plants, similar RNA species termed short-interfering RNAs ''[[siRNA]]s'' are used to prevent the transcription of [[virus|viral]] RNA. While this siRNA is double-stranded, the mechanism seems to be closely related to that of miRNA, especially taking the hairpin structures into account. siRNAs are also used to regulate cellular genes, as miRNAs do.
==Gene activation==
dsRNA can also activate gene expression, a mechanism that has been termed "small RNA-induced gene activation" or [[RNAa]]. dsRNAs targeting gene promoters can induce potent transcriptional activation of associated genes. This was demonstrated in human cells using synthetic dsRNAs termed small activating RNAs ([[saRNA]]s),<ref name= LiLC>{{cite book |chapterurl=http://www.horizonpress.com/rnareg|author= Li LC|year=2008|chapter=Small RNA-Mediated Gene Activation|title=RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity|publisher=Caister Academic Press|id=[http://www.horizonpress.com/rnareg ISBN 978-1-904455-25-7]}}</ref> but has also been demonstrated for endogenous microRNA.<ref>{{cite journal |author=Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R |title=MicroRNA-373 induces expression of genes with complementary promoter sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=105 |issue=5 |pages=1608–13 |year=2008 |pmid=18227514 |doi=10.1073/pnas.0707594105}}</ref>
==Detecting and manipulating miRNA signaling==
The activity of an miRNA can be experimentally blocked using a [[locked nucleic acid]] oligo, a [[Morpholino]] oligo<ref>{{cite journal|url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15585662&query_hl=3|journal=Nucleic Acids Res.|year=2004|month=Dec 7|volume=32|issue=21|pages=6284–91|title=Substrate requirements for let-7 function in the developing zebrafish embryo|last=Kloosterman|first=WP|pmid=15585662|coauthors=Wienholds E, Ketting RF, Plasterk RH|doi=10.1093/nar/gkh968}}</ref><ref>{{cite journal|url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17220889|journal=Nature Genetics|year=2007|volume=39|pages=259–263|title=Zebrafish miR-214 modulates Hedgehog signaling to specify muscle cell fate|last=Flynt|first=AS|pmid=17220889|coauthors=Li N, Thatcher EJ, Solnica-Krezel L, Patton JG|doi=10.1038/ng1953}}</ref>
or a 2'-O-methyl RNA oligo<ref>{{cite journal
|url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14970398&query_hl=13&itool=pubmed_docsum|journal=RNA|year=2004|month=Mar|volume=10|issue=3|pages=544–50|title=Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing|last=Meister|first=G|coauthors=Landthaler M, Dorsett Y, Tuschl T|pmid=14970398|doi=10.1261/rna.5235104}}</ref>. Steps in the maturation of miRNAs can be blocked by steric-blocking oligos<ref>{{cite journal | last = Kloosterman | first = WP | coauthors = Lagendijk AK, Ketting RF, Moulton JD, Plasterk RHA | year = 2007 | title = Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development. | journal = PLoS Biol. | volume = 5 | issue = 8 | pages = e203 | doi = 10.1371/journal.pbio.0050203|format = [[Pubmed]] |pmid=17676975}}</ref>. The target site of an miRNA on an mRNA can be blocked by a steric blocking oligo<ref>{{cite journal | last = Choi | first = WY | coauthors = Giraldez AJ, Schier AF | year = 2007 | title = Target Protectors Reveal Dampening and Balancing of Nodal Agonist and Antagonist by miR-430. | journal = Science. | url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17761850|format = [[Pubmed]] |pmid=17761850}}</ref><ref>{{cite journal | last = Klein | first = ME | coauthors = Lioy DT, Ma L, Impey S, Mandel G, Goodman RH | year = 2007 | title = Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA | journal = Nature Neuroscience | url = http://www.nature.com/neuro/journal/vaop/ncurrent/abs/nn2010.html | doi = 10.1038/nn2010 | volume = 10 | pages = 1513 | format = {{dead link|date=June 2008}} – <sup>[http://scholar.google.co.uk/scholar?hl=en&lr=&q=author%3AKlein+intitle%3AHomeostatic+regulation+of+MeCP2+expression+by+a+CREB-induced+microRNA&as_publication=Nature+Neuroscience&as_ylo=2007&as_yhi=2007&btnG=Search Scholar search]</sup>}}</ref>.
==miRNA and disease==
Just as miRNA is involved in the normal functioning of eukaryotic cells, so has dysregulation of miRNA been associated with disease. Disease association in turn has led to increased funding opportunities for academic research and financial incentives for development and commercialization of miRNA-based diagnostics and therapeutics. After early commercialization aimed at academic research support was established, the initial research focus based on products and services requested was on cancer and neuroscience research. During 2007, interests indicated by product and services requested broadened to include cardiac research, virology, cell biology in general and plant biology.<ref name="2008-Glaser"/>
===miRNA and cancer===
Several miRNAs has been found to have links with some types of [[cancer]].
A study of mice altered to produce excess [[c-myc]] — a protein implicated in several cancers — shows that miRNA has an effect on the development of cancer. Mice that were engineered to produce a surplus of types of miRNA found in [[lymphoma]] cells developed the disease within 50 days and died two weeks later. In contrast, mice without the surplus miRNA lived over 100 days.<ref>{{cite journal
|author=He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM
|title=A microRNA polycistron as a potential human oncogene |journal=[[Nature (journal)|Nature]] |volume=435 |issue=7043| year=2005
|pages=828–833 |pmid=15944707
|doi=10.1038/nature03552
}}</ref>
Another study found that two types of miRNA inhibit the E2F1 protein, which regulates [[Cell growth|cell proliferation]]. miRNA appears to bind to messenger RNA before it can be translated to proteins that switch [[gene]]s on and off.<ref>{{cite journal
|author=O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT |title=c-Myc-regulated microRNAs modulate E2F1 expression
|journal=[[Nature (journal)|Nature]] |volume=435 |issue=7043 |year=2005 |pages=839–843 |pmid=15944709 |doi=10.1038/nature03677
}}</ref>
By measuring activity among 217 genes encoding miRNA, patterns of gene activity that can distinguish types of cancers can be discerned. miRNA signatures may enable classification of cancer. This will allow doctors to determine the original tissue type which spawned a cancer and to be able to target a treatment course based on the original tissue type. miRNA profiling has already been able to determine whether patients with [[chronic lymphocytic leukemia]] had slow growing or aggressive forms of the cancer.<ref>{{cite journal
|author=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
|title=MicroRNA expression profiles classify human cancers |journal=[[Nature (journal)|Nature]] |volume=435 |issue=7043 |year=2005
|pages=834–838 |pmid=15944708
|doi=10.1038/nature03702
}}</ref> In 2008, the companies '''Asuragen''' and '''Exiqon'''<!-- terms redirect to this section --> were working to commercialize this potential for miRNAs to act as cancer [[biomarker]]s.<ref name="2008-Glaser"/><ref>{{cite press release
|title=Exiqon A/S To Acquire Oncotech |publisher=BioSpace
|date=2007-11-27 |url=http://www.biospace.com/news_story.aspx?NewsEntityId=78538 |accessdate=2008-05-16
|quote=The transaction will create a world leader in molecular diagnostic products based on miRNA.
}}</ref>
===miRNA and heart disease===
The global role of miRNA function in the heart has been addressed by conditionally inhibiting miRNA maturation in the [[wikt:murine|murine]] heart, and has revealed that miRNAs play an essential role during its development.<ref>{{cite journal
|author=Chen JF, Murchison EP, Tang R, ''et al''
|title=Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure
|journal=Proc. Natl. Acad. Sci. U.S.A. |volume=105 |issue=6 |pages=2111–2116 |year=2008 |month=February
|pmid=18256189 |doi=10.1073/pnas.0710228105
}}</ref><ref name="2007-Zhao">{{cite journal
|author=Zhao Y, Ransom JF, Li A, ''et al''
|title=Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2
|journal=Cell |volume=129 |issue=2 |pages=303–317 |year=2007 |month=April |pmid=17397913 |doi=10.1016/j.cell.2007.03.030
}}</ref> miRNA expression profiling studies demonstrate that expression levels of specific miRNAs change in diseased human hearts, pointing to their involvement in cardiomyopathies.<ref>{{cite journal
|author=Thum T, Galuppo P, Wolf C, ''et al''
|title=MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure
|journal=Circulation |volume=116 |issue=3 |pages=258–67 |year=2007 |month=July |pmid=17606841 |doi=10.1161/CIRCULATIONAHA.107.687947
}}</ref><ref>{{cite journal
|author=van Rooij E, Sutherland LB, Liu N, ''et al''
|title=A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure
|journal=Proc. Natl. Acad. Sci. U.S.A. |volume=103 |issue=48 |pages=18255–60 |year=2006 |month=November |pmid=17108080
|doi=10.1073/pnas.0608791103
}}</ref><ref>{{cite journal
|author=Tatsuguchi M, Seok HY, Callis TE, ''et al''
|title=Expression of microRNAs is dynamically regulated during cardiomyocyte hypertrophy |journal=J. Mol. Cell. Cardiol.
|volume=42 |issue=6 |pages=1137–41 |year=2007 |month=June |pmid=17498736 |doi=10.1016/j.yjmcc.2007.04.004
}}</ref> Furthermore, studies on specific miRNAs in animal models have 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.<ref name="2007-Zhao"/><ref>{{cite journal
|author=Zhao Y, Samal E, Srivastava D
|title=Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis
|journal=Nature |volume=436 |issue=7048 |pages=214–20 |year=2005 |month=July |pmid=15951802 |doi=10.1038/nature03817
}}</ref><ref>{{cite journal
|author=Xiao J, Luo X, Lin H, ''et al''
|title=MicroRNA miR-133 represses HERG K+ channel expression contributing to QT prolongation in diabetic hearts
|journal=J. Biol. Chem. |volume=282 |issue=17 |pages=12363–7 |year=2007 |month=April |pmid=17344217 |doi=10.1074/jbc.C700015200
}}</ref><ref>{{cite journal
|author=Yang B, Lin H, Xiao J, ''et al''
|title=The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2
|journal=Nat. Med. |volume=13 |issue=4 |pages=486–91 |year=2007 |month=April |pmid=17401374 |doi=10.1038/nm1569
}}</ref><ref>{{cite journal
|author=Carè A, Catalucci D, Felicetti F, ''et al'' |title=MicroRNA-133 controls cardiac hypertrophy
|journal=Nat. Med. |volume=13 |issue=5 |pages=613–8 |year=2007 |month=May |pmid=17468766 |doi=10.1038/nm1582
}}</ref><ref>{{cite journal
|author=van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN
|title=Control of stress-dependent cardiac growth and gene expression by a microRNA |journal=Science (journal) |volume=316
|issue=5824 |pages=575–9 |year=2007 |month=April |pmid=17379774 |doi=10.1126/science.1139089
}}</ref> In 2008, academic work on the relationship between miRNA and heart disease had advanced sufficiently to lead to the establishment of a company, '''miRagen'''<!-- redirect points to this section -->, with a primary focus on "cardiovascular health and disease".<ref name="2008-Glaser">{{cite news
|author=Vicki Glaser |title=Tapping miRNA-Regulated Pathways |url=http://www.genengnews.com/articles/chitem.aspx?aid=2382
|work=Genetic Engineering & Biotechnology News |publisher=Mary Ann Liebert, Inc. |ppg=1, 50, 52—53 |date=2008-03-01 |accessdate=2008-05-16
}}</ref>
==References==
{{reflist|2}}
===Further reading===
* ''This paper discusses the role of microRNAs in viral oncogenesis:'' {{cite journal | author=Scaria V | title=microRNAs in viral oncogenesis. | journal=[[Retrovirology (journal)|Retrovirology]] | volume=4| issue=82| year=2007| pages=68 | doi=10.1186/1742-4690-4-82}}
* ''This paper discusses the role of microRNAs in Host-virus interactions:'' {{cite journal | author=Scaria V | title=Host-Virus Interaction: A new role for microRNAs. | journal=[[Retrovirology (journal)|Retrovirology]] | volume=3| issue=1| year=2006| pages=68 | pmid=17032463 | doi=10.1186/1742-4690-3-68 }}
* ''This paper defines miRNA and proposes guidelines to follow in classifying RNA genes as miRNA:'' {{cite journal | author=Ambros V, Bartel B, Bartel DP, Burge CB, Carrington JC, Chen X, Dreyfuss G, Eddy SR, Griffiths-Jones S, Marshall M, Matzke M, Ruvkun G, Tuschl T | title=A uniform system for microRNA annotation | journal=RNA | volume=9 | issue=3 | year=2003 | pages=277–279 | pmid=12592000 | doi=10.1261/rna.2183803}}
* ''This paper discusses the processes that miRNA and siRNAs are involved in, in the context of 2 articles in the same issue of the journal ''Science'':'' {{cite journal | author=Baulcombe D | title=DNA events. An RNA microcosm. | journal=[[Science (journal)|Science]] | volume=297 | issue=5589 | year=2002 | pages=2002–2003 | pmid=12242426 | doi=10.1126/science.1077906}}
* ''This paper describes the discovery of ''lin-4'', the first miRNA to be discovered:'' {{cite journal | author=Lee RC, Feinbaum RL, Ambros V | title=The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 | journal=Cell | volume=75 | issue=5 | year=1993 | pages=843–854 | pmid=8252621 | doi=10.1016/0092-8674(93)90529-Y}}
==See also==
*[[siRNA]]
*[[Gene expression]]
*[[RNAi]]
*[[Cis-natural Antisense transcripts]]
==External links==
* [http://rnabiology.org RNA Biology] Website of the Council for Scientific and Industrial Research (CSIR), India Network Project on Comparative Genomics of noncoding RNAs.
* [http://genie.weizmann.ac.il/pubs/mir07/mir07_prediction.html PITA] The role of site accessibility in microRNA target recognition, Nature Genetics 2007.
* [http://miracle.igib.res.in/mirex/ miRex: Registry of microRNA expression profiles] Internet registry for microRNA expression profiles. The server is part of [http://miracle.igib.res.in/ RNA@IGIB].
* [http://miracle.igib.res.in/mirfun/ miRfun: microRNA Functional Annotation Server] [Internal Resource].Predicts the functional role of microRNAs based on computational analyses The server is part of [http://miracle.igib.res.in/ RNA@IGIB].
* [http://www.ambion.com/main/explorations/mirna.html A tutorial on miRNAs by Ambion]
* [http://www.rosettagenomics.com/?CategoryID=174 3-D animations describing microRNA formation and function by Rosetta]
* [http://miracle.igib.res.in/eumir/ Eumir: Web server for prediction of eukaryotic microRNA precursors] Web server implementing SVM based prediction of microRNA precursors. Also incorporates companion web server [http://miracle.igib.res.in/hfinder HairpinFetcher].The servers are part of [http://miracle.igib.res.in/ RNA@IGIB].
* [http://mami.med.harvard.edu MAMI - meta-prediction of human microRNA targets] Integrates the leading prediction methods, based on large-scale performance evaluations, into an improved meta-predictor.
* [http://cbit.snu.ac.kr/~ProMiR2/ Probabilistic prediction of microRNAs - ProMiR II]
* [http://miracle.igib.res.in/miracle miRNA target prediction - miRacle server from the RNA@IGIB] The method incorporates structure of the target sequence for prediction of accessibility.
* [http://www.sanger.ac.uk/Software/Rfam/mirna/index.shtml The miRNA Registry]
* [http://miracle.igib.res.in/targetmir.html TargetmiR Infobase of microRNA Targets]
* [http://bibiserv.techfak.uni-bielefeld.de/rnahybrid miRNA target prediction - RNAhybrid]
* [http://www.microrna.org miRNA target prediction - miRanda]
* [http://pictar.bio.nyu.edu miRNA target prediction - PicTar]
* [http://mirna.imbb.forth.gr/microinspector/ miRNA target prediction - MicroInspector]
* [http://www.microrna.org/ micro RNA target search - Human - Drosophila - Zebrafish]
* [http://cbit.snu.ac.kr/~miTarget/ microRNA target prediction using SVM - miTarget]
* [http://miracle.igib.res.in/eumir/ eukaryotic microRNA target prediction using SVM - EumiR]
* [http://miracle.igib.res.in/hfinder/ Algorithm for finding hairpin forming potential of nucleotide sequences- HairpinFetcher]
* [http://tiger.dbs.nus.edu.sg/microtar/ miRNA target prediction - MicroTar]
* [http://cbcsrv.watson.ibm.com/rna22.html microRNA target prediction - The RNA22 algorithm - Any Genome/No Cross-species conservation]
* [http://groups.csail.mit.edu/pag/mirnaminer miRNAminer - a web-based tool for homologous miRNA gene search]
* [http://www.mmmp.org/MMMP/public/biomap/listBiomap.mmmp MicroRNA Biology]
* [http://www.mmmp.org/MMMP/public/biomap/listBiomap.mmmp Oncomirs: the microRNA signature of cancer]
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