Abstract
MicroRNAs (miRNA) are small, naturally occurring single-stranded RNA of about 21–23 nucleotide in length. They are generated from endogenous transcripts that are encoded in the genomes of humans, animals, viruses, and plants. The first short noncoding miRNA, lin-4 that regulates gene expression in nematode C. elegans was identified by Victor Ambros et al. in 1993 [1]. The miRNA world did not take off until the discovery of let-7, a second miRNA discovered by Ruvkun and Horvitz in 2000 [2], and the rise in interest in another class of short RNA, silencing RNA (siRNA) [3, 4]. The highly conserved nature of let-7 also attracted a great deal of attention to miRNA research. Since its discovery, more miRNAs in various organisms, from protozoans to humans have been identified. Currently, a total of 873 miRNAs have been reported in human (miRBase 11.0, April 2008), and many of them are encoded in polycistronic transcripts. The expression of miRNA, in general, is both organ-specific and dependent on the stage of development [5, 6]. miRNAs have diverse functions including regulation of important cellular processes e.g., cancer, cell metabolism, immune function, cell proliferation, apoptosis, tissue development, and differentiation [7–11].
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Reference
Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854
Reinhart BJ, Slack FJ, Basson M et al (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403:901–906
Hamilton AJ, Baulcombe DC (1999) A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286:950–952
Sharp PA, Zamore PD (2000) Molecular biology. RNA interference. Science 287:2431–2433
Lagos-Quintana M, Rauhut R, Yalcin A et al (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol 12:735–739
Houbaviy HB, Murray MF, Sharp PA (2003) Embryonic stem cell-specific MicroRNAs. Dev Cell 5:351–358
Esau C, Davis S, Murray SF et al (2006) miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 3:87–98
Esau C, Kang X, Peralta E et al (2004) MicroRNA-143 regulates adipocyte differentiation. J Biol Chem 279:52361 –52365
Meng F, Henson R, Wehbe-Janek H et al (2007) The MicroRNA let-7a modulates interleukin-6-dependent STAT-3 survival signaling in malignant human cholangiocytes. J Biol Chem 282:8256–8264
Thompson BJ, Cohen SM (2006) The Hippo pathway regulates the bantam microRNA to control cell proliferation and apoptosis in Drosophila. Cell 126:767–774
Alvarez-Garcia I, Miska EA (2005) MicroRNA functions in animal development and human disease. Development 132: 4653–4662
Kim VN (2005) MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 6:376–385
Ketting RF, Fischer SE, Bernstein E et al (2001) Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 15:2654–2659
Lund E, Guttinger S, Calado A et al (2004) Nuclear export of microRNA precursors. Science 303:95–98
Denli AM, Tops BB, Plasterk RH et al (2004) Processing of primary microRNAs by the Microprocessor complex. Nature 432:231–235
Grishok A, Pasquinelli AE, Conte D et al (2001) Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106:23–34
Hammond SM, Bernstein E, Beach D et al (2000) An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404:293–296
Meister G, Landthaler M, Patkaniowska A et al (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 15:185–197
Gregory RI, Yan KP, Amuthan G et al (2004) The Microprocessor complex mediates the genesis of microRNAs. Nature 432:235–240
Rodriguez A, Griffiths-Jones S, Ashurst JL et al (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res 14:1902–1910
Baskerville S, Bartel DP (2005) Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 11:241–247
Calin GA, Sevignani C, Dumitru CD et al (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 101:2999–3004
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Pillai RS, Bhattacharyya SN, Artus CG et al (2005) Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science 309:1573–1576
Mansfield JH, Harfe BD, Nissen R et al (2004) MicroRNA-responsive “sensor” transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nat Genet 36:1079–1083
Yekta S, Shih IH, Bartel DP (2004) MicroRNA-directed cleavage of HOXB8 mRNA. Science 304:594–596
Guo HS, Xie Q, Fei JF et al (2005) MicroRNA directs mRNA cleavage of the transcription factor NAC1 to downregulate auxin signals for arabidopsis lateral root development. Plant Cell 17:1376–1386
Bagga S, Bracht J, Hunter S et al (2005) Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 122:553–563
Jing Q, Huang S, Guth S et al (2005) Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell 120:623–634
Lall S, Grun D, Krek A et al (2006) A genome-wide map of conserved microRNA targets in C. elegans. Curr Biol 16: 460–471
Lewis BP, Shih IH, Jones-Rhoades MW et al (2003) Prediction of mammalian microRNA targets. Cell 115:787–798
Brennecke J, Stark A, Russell RB et al (2005) Principles of microRNA-target recognition. PLoS Biol 3:e85
Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20
Farh KK, Grimson A, Jan C et al (2005) The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science 310:1817–1821
Zeng Y, Wagner EJ, Cullen BR (2002) Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Mol Cell 9: 1327–1333
Chung KH, Hart CC, Al-Bassam S et al (2006) Polycistronic RNA polymerase II expression vectors for RNA interference based on BIC/miR-155. Nucleic Acids Res 34:e53
Krutzfeldt J, Rajewsky N, Braich R et al (2005) Silencing of microRNAs in vivo with “antagomirs”. Nature 438: 685–689
Cheung O, Puri P, Eicken C et al (2008) Nonalcoholic steatohepatitis is associated with altered hepatic microRNA expression. Hepatology 48:1810–1820
Meister G, Landthaler M, Dorsett Y et al (2004) Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing. RNA 10:544–550
Bloomston M, Frankel WL, Petrocca F et al (2007) MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA 297:1901–1908
Ji R, Cheng Y, Yue J et al (2007) MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res 100:1579–1588
Bentwich I (2005) Prediction and validation of microRNAs and their targets. FEBS Lett 579:5904–5910
Gottwein E, Cai X, Cullen BR (2006) A novel assay for viral microRNA function identifies a single nucleotide polymorphism that affects Drosha processing. J Virol 80: 5321–5326
Georgantas RW 3rd, Hildreth R, Morisot S et al (2007) CD34+ hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control. Proc Natl Acad Sci U S A 104:2750–2755
Thermann R, Hentze MW (2007) Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation. Nature 447:875–878
Maroney PA, Yu Y, Fisher J et al (2006) Evidence that microRNAs are associated with translating messenger RNAs in human cells. Nat Struct Mol Biol 13:1102–1107
Nottrott S, Simard MJ, Richter JD (2006) Human let-7a miRNA blocks protein production on actively translating polyribosomes. Nat Struct Mol Biol 13:1108–1114
Pontes O, Pikaard CS (2008) siRNA and miRNA processing: new functions for Cajal bodies. Curr Opin Genet Dev 18:197–203
Anderson P, Kedersha N (2008) Stress granules: the Tao of RNA triage. Trends Biochem Sci 33:141–150
Bhattacharyya SN, Habermacher R, Martine U et al (2006) Stress-induced reversal of microRNA repression and mRNA P-body localization in human cells. Cold Spring Harb Symp Quant Biol 71:513–521
Liu J, Valencia-Sanchez MA, Hannon GJ et al (2005) MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol 7:719–723
Chang J, Nicolas E, Marks D et al (2004) miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol 1:106–113
Reddy JK, Rao MS (2006) Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am J Physiol Gastrointest Liver Physiol 290:G852–G858
Chang J, Guo JT, Jiang D et al (2008) Liver-specific microRNA miR-122 enhances the replication of hepatitis C virus in nonhepatic cells. J Virol 82:8215–8223
Jopling CL, Yi M, Lancaster AM et al (2005) Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 309:1577–1581
Jopling CL, Norman KL, Sarnow P (2006) Positive and negative modulation of viral and cellular mRNAs by liver-specific microRNA miR-122. Cold Spring Harb Symp Quant Biol 71:369–376
Pedersen IM, Cheng G, Wieland S et al (2007) Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449:919–922
Sarasin-Filipowicz M, Krol J, Markiewicz I et al (2009) Decreased levels of miRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy. Nature Med 15:31–33
Kutay H, Bai S, Datta J et al (2006) Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J Cell Biochem 99:671–678
Varnholt H, Drebber U, Schulze F et al (2008) MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma. Hepatology 47:1223–1232
Xie X, Lu J, Kulbokas EJ et al (2005) Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals. Nature 434:338–345
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Cheung, O., Sanyal, A.J. (2010). MicroRNAs. In: Dufour, JF., Clavien, PA. (eds) Signaling Pathways in Liver Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00150-5_33
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DOI: https://doi.org/10.1007/978-3-642-00150-5_33
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