OALib Journal期刊
ISSN: 2333-9721
费用：99美元

投递稿件

查看量	下载量

相关文章
更多...

Biology 2013

MicroRNA Target Identification—Experimental Approaches

DOI: 10.3390/biology2010189

Aida Martinez-Sanchez,Chris L. Murphy

Keywords: miRNA, gene expression, miRISC, miRNA target identification, RIP-Seq, HITS-CLIP, HT-Seq

Full-Text Cite this paper Add to My Lib

Abstract:

MicroRNAs (miRNAs) are small non-coding RNA molecules of 21–23 nucleotides that control gene expression at the post-transcriptional level. They have been shown to play a vital role in a wide variety of biological processes and dysregulated expression of miRNAs is observed in many pathologies. Understanding the mechanism of action and identifying functionally important mRNA targets of a specific miRNA are essential to unravelling its biological function and to assist miRNA-based drug development. This review summarizes the current understanding of the mechanistic aspects of miRNA-mediated gene repression and focuses on the different approaches for miRNA target identification that have been proposed in recent years.

References

[1]	Ambros, V. The functions of animal micrornas. Nature 2004, 431, 350–355, doi:10.1038/nature02871.
[2]	Small, E.M.; Olson, E.N. Pervasive roles of micrornas in cardiovascular biology. Nature 2011, 469, 336–342, doi:10.1038/nature09783.
[3]	Lujambio, A.; Lowe, S.W. The microcosmos of cancer. Nature 2012, 482, 347–355, doi:10.1038/nature10888.
[4]	Mendell, J.T.; Olson, E.N. Micrornas in stress signaling and human disease. Cell 2012, 148, 1172–1187, doi:10.1016/j.cell.2012.02.005.
[5]	Lee, Y.; Kim, M.; Han, J.; Yeom, K.H.; Lee, S.; Baek, S.H.; Kim, V.N. Microrna genes are transcribed by rna polymerase ii. EMBO J. 2004, 23, 4051–4060, doi:10.1038/sj.emboj.7600385.
[6]	Rodriguez, A.; Griffiths-Jones, S.; Ashurst, J.L.; Bradley, A. Identification of mammalian microrna host genes and transcription units. Genome Res. 2004, 14, 1902–1910, doi:10.1101/gr.2722704.
[7]	Kim, V.N.; Han, J.; Siomi, M.C. Biogenesis of small rnas in animals. Nat. Rev. Mol. Cell Biol. 2009, 10, 126–139.
[8]	Yang, J.S.; Lai, E.C. Alternative mirna biogenesis pathways and the interpretation of core mirna pathway mutants. Mol. Cell 2011, 43, 892–903.
[9]	Chiang, H.R.; Schoenfeld, L.W.; Ruby, J.G.; Auyeung, V.C.; Spies, N.; Baek, D.; Johnston, W.K.; Russ, C.; Luo, S.; Babiarz, J.E.; et al. Mammalian micrornas: Experimental evaluation of novel and previously annotated genes. Genes Dev. 2010, 24, 992–1009, doi:10.1101/gad.1884710.
[10]	Czech, B.; Hannon, G.J. Small RNA sorting: Matchmaking for argonautes. Nat. Rev. Genet. 2011, 12, 19–31.
[11]	Wang, B.; Li, S.; Qi, H.H.; Chowdhury, D.; Shi, Y.; Novina, C.D. Distinct passenger strand and mrna cleavage activities of human argonaute proteins. Nat. Struct. Mol. Biol. 2009, 16, 1259–1266, doi:10.1038/nsmb.1712.
[12]	Pasquinelli, A.E. Micrornas and their targets: Recognition, regulation and an emerging reciprocal relationship. Nat. Rev. Genet. 2012, 13, 271–282.
[13]	Bartel, D.P. Micrornas: Target recognition and regulatory functions. Cell 2009, 136, 215–233, doi:10.1016/j.cell.2009.01.002.
[14]	Shin, C.; Nam, J.W.; Farh, K.K.; Chiang, H.R.; Shkumatava, A.; Bartel, D.P. Expanding the microrna targeting code: Functional sites with centered pairing. Mol. Cell 2010, 38, 789–802.
[15]	Lal, A.; Navarro, F.; Maher, C.A.; Maliszewski, L.E.; Yan, N.; O’Day, E.; Chowdhury, D.; Dykxhoorn, D.M.; Tsai, P.; Hofmann, O.; et al. Mir-24 inhibits cell proliferation by targeting e2f2, myc, and other cell-cycle genes via binding to “seedless” 3'utr microrna recognition elements. Mol. Cell 2009, 35, 610–625, doi:10.1016/j.molcel.2009.08.020.
[16]	Hafner, M.; Landthaler, M.; Burger, L.; Khorshid, M.; Hausser, J.; Berninger, P.; Rothballer, A.; Ascano, M., Jr.; Jungkamp, A.C.; Munschauer, M.; et al. Transcriptome-wide identification of rna-binding protein and microrna target sites by par-clip. Cell 2010, 141, 129–141, doi:10.1016/j.cell.2010.03.009.
[17]	Kedde, M.; Strasser, M.J.; Boldajipour, B.; Oude Vrielink, J.A.; Slanchev, K.; le Sage, C.; Nagel, R.; Voorhoeve, P.M.; van Duijse, J.; Orom, U.A.; et al. Rna-binding protein dnd1 inhibits microrna access to target mrna. Cell 2007, 131, 1273–1286, doi:10.1016/j.cell.2007.11.034.
[18]	Kundu, P.; Fabian, M.R.; Sonenberg, N.; Bhattacharyya, S.N.; Filipowicz, W. Hur protein attenuates mirna-mediated repression by promoting mirisc dissociation from the target RNA. Nucleic Acids Res. 2012, 40, 5088–5100, doi:10.1093/nar/gks148.
[19]	Witkos, T.M.; Koscianska, E.; Krzyzosiak, W.J. Practical aspects of microrna target prediction. Curr. Mol. Med. 2011, 11, 93–109, doi:10.2174/156652411794859250.
[20]	Alexiou, P.; Maragkakis, M.; Papadopoulos, G.L.; Reczko, M.; Hatzigeorgiou, A.G. Lost in translation: An assessment and perspective for computational microrna target identification. Bioinformatics 2009, 25, 3049–3055, doi:10.1093/bioinformatics/btp565.
[21]	Long, J.M.; Lahiri, D.K. Advances in microrna experimental approaches to study physiological regulation of gene products implicated in cns disorders. Exp. Neurol. 2012, 235, 402–418, doi:10.1016/j.expneurol.2011.12.043.
[22]	Huntzinger, E.; Izaurralde, E. Gene silencing by micrornas: Contributions of translational repression and mrna decay. Nat. Rev. Genet. 2011, 12, 99–110, doi:10.1038/nrg2936.
[23]	Gebauer, F.; Hentze, M.W. Molecular mechanisms of translational control. Nat. Rev. Mol. Cell Biol. 2004, 5, 827–835, doi:10.1038/nrm1488.
[24]	Pillai, R.S.; Bhattacharyya, S.N.; Artus, C.G.; Zoller, T.; Cougot, N.; Basyuk, E.; Bertrand, E.; Filipowicz, W. Inhibition of translational initiation by let-7 microrna in human cells. Science 2005, 309, 1573–1576, doi:10.1126/science.1115079.
[25]	Humphreys, D.T.; Westman, B.J.; Martin, D.I.; Preiss, T. Micrornas control translation initiation by inhibiting eukaryotic initiation factor 4e/cap and poly(a) tail function. Proc. Natl. Acad. Sci. USA 2005, 102, 16961–16966.
[26]	Petersen, C.P.; Bordeleau, M.E.; Pelletier, J.; Sharp, P.A. Short RNAs repress translation after initiation in mammalian cells. Mol. Cell 2006, 21, 533–542, doi:10.1016/j.molcel.2006.01.031.
[27]	Filipowicz, W.; Bhattacharyya, S.N.; Sonenberg, N. Mechanisms of post-transcriptional regulation by micrornas: Are the answers in sight? Nat. Rev. Genet. 2008, 9, 102–114.
[28]	Mathonnet, G.; Fabian, M.R.; Svitkin, Y.V.; Parsyan, A.; Huck, L.; Murata, T.; Biffo, S.; Merrick, W.C.; Darzynkiewicz, E.; Pillai, R.S.; et al. Microrna inhibition of translation initiation in vitro by targeting the cap-binding complex eif4f. Science 2007, 317, 1764–1767.
[29]	Nottrott, S.; Simard, M.J.; Richter, J.D. Human let-7a mirna blocks protein production on actively translating polyribosomes. Nat. Struct. Mol. Biol. 2006, 13, 1108–1114, doi:10.1038/nsmb1173.
[30]	Braun, J.E.; Huntzinger, E.; Fauser, M.; Izaurralde, E. Gw182 proteins directly recruit cytoplasmic deadenylase complexes to mirna targets. Mol. Cell 2011, 44, 120–133, doi:10.1016/j.molcel.2011.09.007.
[31]	Fabian, M.R.; Cieplak, M.K.; Frank, F.; Morita, M.; Green, J.; Srikumar, T.; Nagar, B.; Yamamoto, T.; Raught, B.; Duchaine, T.F.; et al. Mirna-mediated deadenylation is orchestrated by gw182 through two conserved motifs that interact with ccr4-not. Nat. Struct. Mol. Biol. 2011, 18, 1211–1217.
[32]	Baek, D.; Villen, J.; Shin, C.; Camargo, F.D.; Gygi, S.P.; Bartel, D.P. The impact of microRNAs on protein output. Nature 2008, 455, 64–71, doi:10.1038/nature07242.
[33]	Hendrickson, D.G.; Hogan, D.J.; McCullough, H.L.; Myers, J.W.; Herschlag, D.; Ferrell, J.E.; Brown, P.O. Concordant regulation of translation and mrna abundance for hundreds of targets of a human microrna. PLoS Biol. 2009, 7, e1000238.
[34]	Guo, H.; Ingolia, N.T.; Weissman, J.S.; Bartel, D.P. Mammalian micrornas predominantly act to decrease target mrna levels. Nature 2010, 466, 835–840, doi:10.1038/nature09267.
[35]	Selbach, M.; Schwanhausser, B.; Thierfelder, N.; Fang, Z.; Khanin, R.; Rajewsky, N. Widespread changes in protein synthesis induced by micrornas. Nature 2008, 455, 58–63.
[36]	Fabian, M.R.; Sonenberg, N. The mechanics of mirna-mediated gene silencing: A look under the hood of mirisc. Nat. Struct. Mol. Biol. 2012, 19, 586–593, doi:10.1038/nsmb.2296.
[37]	Grimson, A.; Farh, K.K.; Johnston, W.K.; Garrett-Engele, P.; Lim, L.P.; Bartel, D.P. MicroRNA targeting specificity in mammals: Determinants beyond seed pairing. Mol. Cell 2007, 27, 91–105.
[38]	Lewis, B.P.; Burge, C.B.; Bartel, D.P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005, 120, 15–20, doi:10.1016/j.cell.2004.12.035.
[39]	Long, D.; Lee, R.; Williams, P.; Chan, C.Y.; Ambros, V.; Ding, Y. Potent effect of target structure on microrna function. Nat. Struct. Mol. Biol. 2007, 14, 287–294, doi:10.1038/nsmb1226.
[40]	Chi, S.W.; Hannon, G.J.; Darnell, R.B. An alternative mode of microrna target recognition. Nat. Struct. Mol. Biol. 2012, 19, 321–327, doi:10.1038/nsmb.2230.
[41]	Sethupathy, P.; Megraw, M.; Hatzigeorgiou, A.G. A guide through present computational approaches for the identification of mammalian microrna targets. Nat. Methods 2006, 3, 881–886.
[42]	DIANA-microT. Available online: http://diana.cslab.ece.ntua.gr/microT/ (accessed on 1 January 2013).
[43]	DIANA-microT-CDS. Available online: http://diana.cslab.ece.ntua.gr/micro-CDS/ (accessed on 1 January 2013).
[44]	MicroInspector. Available online: http://bioinfo.uni-plovdiv.bg/microinspector/ (accessed on 1 January 2013).
[45]	MiRanda. Available online: http://www.microrna.org/ (accessed on 1 January 2013).
[46]	Pictar. Available online: http://pictar.mdc-berlin.de/ (accessed on 1 January 2013).
[47]	RNA22. Available online: http://cbcsrv.watson.ibm.com/rna22.html/ (accessed on 1 January 2013).
[48]	RNAhybrid. Available online: http://bibiserv.techfak.uni-bielefeld.de/rnahybrid/ (accessed on 1 January 2013).
[49]	TargetScan (v6), Available online: http://www.targetscan.org/ (accessed on 1 January 2013).
[50]	Kozomara, A.; Griffiths-Jones, S. Mirbase: Integrating microrna annotation and deep-sequencing data. Nucleic Acids Res. 2011, 39, D152–D157, doi:10.1093/nar/gkq1027.
[51]	Megraw, M.; Sethupathy, P.; Corda, B.; Hatzigeorgiou, A.G. Mirgen: A database for the study of animal microrna genomic organization and function. Nucleic Acids Res. 2007, 35, D149–D155, doi:10.1093/nar/gkl904.
[52]	Vergoulis, T.; Vlachos, I.S.; Alexiou, P.; Georgakilas, G.; Maragkakis, M.; Reczko, M.; Gerangelos, S.; Koziris, N.; Dalamagas, T.; Hatzigeorgiou, A.G. 0: Capturing the exponential growth of miRNA targets with experimental support. Nucleic Acids Res. 2012, 40, D222–D229.
[53]	Hsu, S.D.; Chu, C.H.; Tsou, A.P.; Chen, S.J.; Chen, H.C.; Hsu, P.W.; Wong, Y.H.; Chen, Y.H.; Chen, G.H.; Huang, H.D. Mirnamap 2.0: Genomic maps of micrornas in metazoan genomes. Nucleic Acids Res. 2008, 36, D165–D169.
[54]	Rajewsky, N. Microrna target predictions in animals. Nat. Genet. 2006, 38, S8–S13, doi:10.1038/ng1798.
[55]	Ebert, M.S.; Sharp, P.A. Roles for micrornas in conferring robustness to biological processes. Cell 2012, 149, 515–524, doi:10.1016/j.cell.2012.04.005.
[56]	rom, U.A.; Lund, A.H. Experimental identification of microrna targets. Gene 2010, 451, 1–5, doi:10.1016/j.gene.2009.11.008.
[57]	Thomas, M.; Lieberman, J.; Lal, A. Desperately seeking microrna targets. Nat. Struct. Mol. Biol. 2010, 17, 1169–1174.
[58]	Lim, L.P.; Lau, N.C.; Garrett-Engele, P.; Grimson, A.; Schelter, J.M.; Castle, J.; Bartel, D.P.; Linsley, P.S.; Johnson, J.M. Microarray analysis shows that some micrornas downregulate large numbers of target mrnas. Nature 2005, 433, 769–773.
[59]	Linsley, P.S.; Schelter, J.; Burchard, J.; Kibukawa, M.; Martin, M.M.; Bartz, S.R.; Johnson, J.M.; Cummins, J.M.; Raymond, C.K.; Dai, H.; et al. Transcripts targeted by the microrna-16 family cooperatively regulate cell cycle progression. Mol. Cell Biol. 2007, 27, 2240–2252.
[60]	Krützfeldt, J.; Rajewsky, N.; Braich, R.; Rajeev, K.G.; Tuschl, T.; Manoharan, M.; Stoffel, M. Silencing of micrornas in vivo with “antagomirs”. Nature 2005, 438, 685–689.
[61]	Elmén, J.; Lindow, M.; Silahtaroglu, A.; Bak, M.; Christensen, M.; Lind-Thomsen, A.; Hedtj？rn, M.; Hansen, J.B.; Hansen, H.F.; Straarup, E.M.; et al. Antagonism of microrna-122 in mice by systemically administered lna-antimir leads to up-regulation of a large set of predicted target mrnas in the liver. Nucleic Acids Res. 2008, 36, 1153–1162.
[62]	Xu, G.; Fewell, C.; Taylor, C.; Deng, N.; Hedges, D.; Wang, X.; Zhang, K.; Lacey, M.; Zhang, H.; Yin, Q.; et al. Transcriptome and targetome analysis in mir155 expressing cells using rna-seq. RNA 2010, 16, 1610–1622, doi:10.1261/rna.2194910.
[63]	Vinther, J.; Hedegaard, M.M.; Gardner, P.P.; Andersen, J.S.; Arctander, P. Identification of mirna targets with stable isotope labeling by amino acids in cell culture. Nucleic Acids Res. 2006, 34, e107.
[64]	Kaller, M.; Liffers, S.T.; Oeljeklaus, S.; Kuhlmann, K.; R？h, S.; Hoffmann, R.; Warscheid, B.; Hermeking, H. Genome-wide characterization of mir-34a induced changes in protein and mrna expression by a combined pulsed silac and microarray analysis. Mol. Cell. Proteomics 2011, 10, M111.010462, doi:10.1074/mcp.M111.010462.
[65]	Ingolia, N.T.; Ghaemmaghami, S.; Newman, J.R.; Weissman, J.S. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 2009, 324, 218–223.
[66]	Bazzini, A.A.; Lee, M.T.; Giraldez, A.J. Ribosome profiling shows that mir-430 reduces translation before causing mrna decay in zebrafish. Science 2012, 336, 233–237.
[67]	Landthaler, M.; Gaidatzis, D.; Rothballer, A.; Chen, P.Y.; Soll, S.J.; Dinic, L.; Ojo, T.; Hafner, M.; Zavolan, M.; Tuschl, T. Molecular characterization of human argonaute-containing ribonucleoprotein complexes and their bound target mrnas. RNA 2008, 14, 2580–2596.
[68]	Ding, L.; Han, M. Gw182 family proteins are crucial for microrna-mediated gene silencing. Trends Cell Biol. 2007, 17, 411–416.
[69]	rom, U.A.; Nielsen, F.C.; Lund, A.H. Microrna-10a binds the 5' utr of ribosomal protein mrnas and enhances their translation. Mol. Cell 2008, 30, 460–471.
[70]	Hsu, R.J.; Tsai, H.J. Performing the labeled microrna pull-down (lamp) assay system: An experimental approach for high-throughput identification of microrna-target mrnas. Methods Mol. Biol. 2011, 764, 241–247.
[71]	Baigude, H.; Ahsanullah; Li, Z.; Zhou, Y.; Rana, T.M. Mir-trap: A benchtop chemical biology strategy to identify microrna targets. Angew Chem. Int. Ed. Engl. 2012, 51, 5880–5883.
[72]	Yoon, J.H.; Srikantan, S.; Gorospe, M. Ms2-trap (ms2-tagged rna affinity purification): Tagging rna to identify associated mirnas. Methods 2012, 58, 81–87.
[73]	Keene, J.D.; Komisarow, J.M.; Friedersdorf, M.B. Rip-chip: The isolation and identification of mrnas, micrornas and protein components of ribonucleoprotein complexes from cell extracts. Nat. Protoc. 2006, 1, 302–307.
[74]	Baroni, T.E.; Chittur, S.V.; George, A.D.; Tenenbaum, S.A. Advances in rip-chip analysis: Rna-binding protein immunoprecipitation-microarray profiling. Methods Mol. Biol. 2008, 419, 93–108.
[75]	Karginov, F.V.; Conaco, C.; Xuan, Z.; Schmidt, B.H.; Parker, J.S.; Mandel, G.; Hannon, G.J. A biochemical approach to identifying microrna targets. Proc. Natl. Acad. Sci. USA 2007, 104, 19291–19296.
[76]	Tan, L.P.; Seinen, E.; Duns, G.; de Jong, D.; Sibon, O.C.; Poppema, S.; Kroesen, B.J.; Kok, K.; van den Berg, A. A high throughput experimental approach to identify miRNA targets in human cells. Nucleic Acids Res. 2009, 37, e137.
[77]	Beitzinger, M.; Peters, L.; Zhu, J.Y.; Kremmer, E.; Meister, G. Identification of human microrna targets from isolated argonaute protein complexes. RNA Biol. 2007, 4, 76–84.
[78]	Su, H.; Trombly, M.I.; Chen, J.; Wang, X. Essential and overlapping functions for mammalian argonautes in microrna silencing. Genes Dev. 2009, 23, 304–317.
[79]	Nelson, P.T.; de Planell-Saguer, M.; Lamprinaki, S.; Kiriakidou, M.; Zhang, P.; O'Doherty, U.; Mourelatos, Z. A novel monoclonal antibody against human argonaute proteins reveals unexpected characteristics of mirnas in human blood cells. RNA 2007, 13, 1787–1792.
[80]	Zhang, L.; Ding, L.; Cheung, T.H.; Dong, M.Q.; Chen, J.; Sewell, A.K.; Liu, X.; Yates, J.R.; Han, M. Systematic identification of C. elegans mirisc proteins, mirnas, and mrna targets by their interactions with gw182 proteins ain-1 and ain-2. Mol. Cell 2007, 28, 598–613, doi:10.1016/j.molcel.2007.09.014.
[81]	Chi, S.W.; Zang, J.B.; Mele, A.; Darnell, R.B. Argonaute hits-clip decodes microRNA-mRNA interaction maps. Nature 2009, 460, 479–486.
[82]	Licatalosi, D.D.; Mele, A.; Fak, J.J.; Ule, J.; Kayikci, M.; Chi, S.W.; Clark, T.A.; Schweitzer, A.C.; Blume, J.E.; Wang, X.; et al. Hits-clip yields genome-wide insights into brain alternative RNA processing. Nature 2008, 456, 464–469, doi:10.1038/nature07488.
[83]	Hafner, M.; Lianoglou, S.; Tuschl, T.; Betel, D. Genome-wide identification of mirna targets by par-clip. Methods 2012, 58, 94–105.
[84]	Zhang, C.; Darnell, R.B. Mapping in vivo protein-RNA interactions at single-nucleotide resolution from hits-clip data. Nat. Biotechnol. 2011, 29, 607–614, doi:10.1038/nbt.1873.
[85]	Martinez-Sanchez, A.; Dudek, K.A.; Murphy, C.L. Regulation of human chondrocyte function through direct inhibition of cartilage master regulator sox9 by microrna-145 (mirna-145). J. Biol. Chem. 2012, 287, 916–924.
[86]	Lee, R.C.; Feinbaum, R.L.; Ambros, V. The C. elegans heterochronic gene lin-4 encodes small rnas with antisense complementarity to lin-14. Cell 1993, 75, 843–854, doi:10.1016/0092-8674(93)90529-Y.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133