A study of miRNAs targets prediction and experimental validation

Yong Huang1,3, Quan Zou2, Haitai Song1,3, Fei Song1,3, Ligang Wang1,3, Guozheng Zhang1,3, Xingjia Shen1,3()

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Protein Cell ›› 2010, Vol. 1 ›› Issue (11) : 979-986. DOI: 10.1007/s13238-010-0129-4
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A study of miRNAs targets prediction and experimental validation

  • Yong Huang1,3, Quan Zou2, Haitai Song1,3, Fei Song1,3, Ligang Wang1,3, Guozheng Zhang1,3, Xingjia Shen1,3()
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Abstract

microRNAs (miRNAs) are 20–24 nucleotide (nt) RNAs that regulate eukaryotic gene expression post-transcriptionally by the degradation or translational inhibition of their target messenger RNAs (mRNAs). To identify miRNA target genes will help a lot by understanding their biological functions. Sophisticated computational approaches for miRNA target prediction, and effective biological techniques for validating these targets now play a central role in elucidating their functions. Owing to the imperfect complementarity of animal miRNAs with their targets, it is difficult to judge the accuracy of the prediction. Complexity of regulation by miRNA-mediated targets at protein and mRNAs levels has made it more challenging to identify the targets. To date, only a few miRNAs targets are confirmed. In this article, we review the methods of miRNA target prediction and the experimental validation for their corresponding mRNA targets in animals.

Keywords

microRNA / computational prediction / target / experimental validation

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Yong Huang, Quan Zou, Haitai Song, Fei Song, Ligang Wang, Guozheng Zhang, Xingjia Shen. A study of miRNAs targets prediction and experimental validation. Prot Cell, 2010, 1(11): 979‒986 https://doi.org/10.1007/s13238-010-0129-4

References

[1] Aravin, A., and Tuschl, T. (2005). Identification and characterization of small RNAs involved in RNA silencing. FEBS Lett 579, 5830-5840 .10.1016/j.febslet.2005.08.009
[2] Baek, D., Villén, J., Shin, C., Camargo, F.D., Gygi, S.P., and Bartel, D.P. (2008). The impact of microRNAs on protein output. Nature 455, 64-71 .10.1038/nature07242
[3] Banerjee, S., Wang, Z., Mohammad, M., Sarkar, F.H., and Mohammad, R.M. (2008). Efficacy of selected natural products as therapeutic agents against cancer. J Nat Prod 71, 492-496 .10.1021/np0705716
[4] Bartel, D.P. (2009). MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233 .
[5] Beitzinger, M., Peters, L., Zhu, J.Y., Kremmer, E., and Meister, G. (2007). Identification of human microRNA targets from isolated argonaute protein complexes. RNA Biol 4, 76-84 .
[6] Boissonneault, V., St-Gelais, N., Plante, I., and Provost, P. (2008). A polymerase chain reaction-based cloning strategy applicable to functional microRNA studies. Anal Biochem 381, 166-168 .10.1016/j.ab.2008.06.026
[7] Brennecke, J., Stark, A., Russell, R.B., and Cohen, S.M. (2005). Principles of microRNA-target recognition. PLoS Biol 3, e85.10.1371/journal.pbio.0030085
[8] Brodersen, P., and Voinnet, O. (2009). Revisiting the principles of microRNA target recognition and mode of action. Nat Rev Mol Cell Biol 10, 141-148 .10.1038/nrm2619
[9] Cai, X., Hagedorn, C.H., and Cullen, B.R. (2004). Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10, 1957-1966 .
[10] Chi, S.W., Zang, J.B., Mele, A., and Darnell, R.B. (2009). Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature 460, 479-486 .
[11] Easow, G., Teleman, A.A., and Cohen, S.M. (2007). Isolation of microRNA targets by miRNP immunopurification. RNA 13, 1198-1204 .
[12] Elbashir, S.M., Lendeckel, W., and Tuschl, T. (2001). RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev 15, 188-200 .10.1101/gad.862301
[13] Engels, B.M., and Hutvagner, G. (2006). Principles and effects of microRNA-mediated post-transcriptional gene regulation. Oncogene 25, 6163-6169 .10.1038/sj.onc.1209909
[14] Enright, A.J., John, B., Gaul, U., Tuschl, T., Sander, C., and Marks, D.S. (2003). MicroRNA targets in Drosophila. Genome Biol 5, R1.10.1186/gb-2003-5-1-r1
[15] Flynt, A.S., and Lai, E.C. (2008). Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet 9, 831-842 .10.1038/nrg2455
[16] Friedman, R.C., Farh, K.K., Burge, C.B., and Bartel, D.P. (2009). Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19, 92-105 .10.1101/gr.082701.108
[17] Gaidatzis, D., van Nimwegen, E., Hausser, J., and Zavolan, M. (2007). Inference of miRNA targets using evolutionary conservation and pathway analysis. BMC Bioinformatics 8, 69.10.1186/1471-2105-8-69
[18] Hafner, M., Landthaler, M., Burger, L., Khorshid, M., Hausser, J., Berninger, P., Rothballer, A., Ascano, M. Jr, Jungkamp, A.C., Munschauer, M., . (2010). Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141, 129-141 .
[19] Hammell, M., Long, D., Zhang, L., Lee, A., Carmack, C.S., Han, M., Ding, Y., and Ambros, V. (2008). mirWIP: microRNA target prediction based on microRNA-containing ribonucleoprotein-enriched transcripts. Nat Methods 5, 813-819 .10.1038/nmeth.1247
[20] Hassan, M.Q., Gordon, J.A., Lian, J.B., van Wijnen, A.J., Stein, J.L., and Stein, G.S. (2010). Ribonucleoprotein immunoprecipitation (RNP-IP): a direct in vivo analysis of microRNA-targets. J Cell Biochem 110, 817-822 .10.1002/jcb.22562
[21] Huang, J.C., Babak, T., Corson, T.W., Chua, G., Khan, S., Gallie, B.L., Hughes, T.R., Blencowe, B.J., Frey, B.J., and Morris, Q.D. (2007). Using expression profiling data to identify human microRNA targets. Nat Methods 4, 1045-1049 .10.1038/nmeth1130
[22] Hutvágner, G., and Zamore, P.D. (2002). A microRNA in a multiple-turnover RNAi enzyme complex. Science 297, 2056-2060 .10.1126/science.1073827
[23] Hwang, H.W., and Mendell, J.T. (2007). MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer 96, R40-R44 .
[24] Ivanovska, I., and Cleary, M.A. (2008). Combinatorial microRNAs: working together to make a difference. Cell Cycle 7, 3137-3142 .
[25] John, B., Enright, A.J., Aravin, A., Tuschl, T., Sander, C., and Marks, D.S. (2004). Human MicroRNA targets. PLoS Biol 2, e363.10.1371/journal.pbio.0020363
[26] Johnson, S.M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K.L., Brown, D., and Slack, F.J. (2005). RAS is regulated by the let-7 microRNA family. Cell 120, 635-647 .
[27] Johnston, R.J. Jr, and Hobert, O. (2003). A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature 426, 845-849 .10.1038/nature02255
[28] Kertesz, M., Iovino, N., Unnerstall, U., Gaul, U., and Segal, E. (2007). The role of site accessibility in microRNA target recognition. Nat Genet 39, 1278-1284 .10.1038/ng2135
[29] Kim, S.K., Nam, J.W., Rhee, J.K., Lee, W.J., and Zhang, B.T. (2006). miTarget: microRNA target gene prediction using a support vector machine. BMC Bioinformatics 7, 411.10.1186/1471-2105-7-411
[30] Kim, V.N. (2004). MicroRNA precursors in motion: exportin-5 mediates their nuclear export. Trends Cell Biol 14, 156-159 .10.1016/j.tcb.2004.02.006
[31] Kiriakidou, M., Nelson, P.T., Kouranov, A., Fitziev, P., Bouyioukos, C., Mourelatos, Z., and Hatzigeorgiou, A. (2004). A combined computational-experimental approach predicts human microRNA targets. Genes Dev 18, 1165-1178 .10.1101/gad.1184704
[32] Krek, A., Grün, D., Poy, M.N., Wolf, R., Rosenberg, L., Epstein, E.J., MacMenamin, P., da Piedade, I., Gunsalus, K.C., Stoffel, M., . (2005). Combinatorial microRNA target predictions. Nat Genet 37, 495-500 .10.1038/ng1536
[33] Krüger, J., and Rehmsmeier, M. (2006). RNAhybrid: microRNA target prediction easy, fast and flexible. Nucleic Acids Res 34, W451-454 .
[34] Lee, I., Ajay, S.S., Yook, J.I., Kim, H.S., Hong, S.H., Kim, N.H., Dhanasekaran, S.M., Chinnaiyan, A.M., and Athey, B.D. (2009). New class of microRNA targets containing simultaneous 5′-UTR and 3′-UTR interaction sites. Genome Res 19, 1175-1183 .10.1101/gr.089367.108
[35] Lee, J.Y., Kim, S., Hwang, W., Jeong, J.M., Chung, J.K., Lee, M.C., and Lee, D.S. (2008). Development of a dual-luciferase reporter system for in vivo visualization of MicroRNA biogenesis and posttranscriptional regulation. J Nucl Med 49, 285-294 .10.2967/jnumed.107.042507
[36] Lee, R.C., Feinbaum, R.L., and Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854 .
[37] Lee, Y., Ahn, C., Han, J., Choi, H., Kim, J., Yim, J., Lee, J., Provost, P., R?dmark, O., Kim, S., . (2003). The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415-419 .10.1038/nature01957
[38] Lee, Y., Kim, M., Han, J., Yeom, K.H., Lee, S., Baek, S.H., and Kim, V.N. (2004). MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23, 4051-4060 .10.1038/sj.emboj.7600385
[39] Lewis, B.P., Burge, C.B., and Bartel, D.P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20 .
[40] Lewis, B.P., Shih, I.H., Jones-Rhoades, M.W., Bartel, D.P., and Burge, C.B. (2003). Prediction of mammalian microRNA targets. Cell 115, 787-798 .
[41] Liu, Q., Fu, H., Sun, F., Zhang, H., Tie, Y., Zhu, J., Xing, R., Sun, Z., and Zheng, X. (2008). miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes. Nucleic Acids Res 36, 5391-5404 .10.1093/nar/gkn522
[42] Lund, E., Güttinger, S., Calado, A., Dahlberg, J.E., and Kutay, U. (2004). Nuclear export of microRNA precursors. Science 303, 95-98 .10.1126/science.1090599
[43] Ma, L., Teruya-Feldstein, J., and Weinberg, R.A. (2007). Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449, 682-688 .10.1038/nature06174
[44] Maragkakis, M., Alexiou, P., Papadopoulos, G.L., Reczko, M., Dalamagas, T., Giannopoulos, G., Goumas, G., Koukis, E., Kourtis, K., Simossis, V.A., . (2009a). Accurate microRNA target prediction correlates with protein repression levels. BMC Bioinformatics 10, 295.10.1186/1471-2105-10-295
[45] Maragkakis, M., Reczko, M., Simossis, V.A., Alexiou, P., Papadopoulos, G.L., Dalamagas, T., Giannopoulos, G., Goumas, G., Koukis, E., Kourtis, K., . (2009b). DIANA-microT web server: elucidating microRNA functions through target prediction. Nucleic Acids Res 37, W273-276 .10.1093/nar/gkp292
[46] Min, H., and Yoon, S. (2010). Got target? Computational methods for microRNA target prediction and their extension. Exp Mol Med 42, 233-244 .10.3858/emm.2010.42.4.032
[47] Miranda, K.C., Huynh, T., Tay, Y., Ang, Y.S., Tam, W.L., Thomson, A.M., Lim, B., and Rigoutsos, I. (2006). A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell 126, 1203-1217 .
[48] Nachmani, D., Stern-Ginossar, N., Sarid, R., and Mandelboim, O. (2009). Diverse herpesvirus microRNAs target the stress-induced immune ligand MICB to escape recognition by natural killer cells. Cell Host Microbe 5, 376-385 .10.1016/j.chom.2009.03.003
[49] Nonne, N., Ameyar-Zazoua, M., Souidi, M., and Harel-Bellan, A. (2010). Tandem affinity purification of miRNA target mRNAs (TAP-Tar). Nucleic Acids Res 38, e20.10.1093/nar/gkp1100
[50] O’Donnell, K.A., Wentzel, E.A., Zeller, K.I., Dang, C.V., and Mendell, J.T. (2005). c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435, 839-843 .10.1038/nature03677
[51] ?rom, U.A., and Lund, A.H. (2010). Experimental identification of microRNA targets. Gene 451, 1-5 .
[52] Pillai, R.S. (2005). MicroRNA function: multiple mechanisms for a tiny RNA? RNA 11, 1753-1761 .
[53] Poy, M.N., Eliasson, L., Krutzfeldt, J., Kuwajima, S., Ma, X., Macdonald, P.E., Pfeffer, S., Tuschl, T., Rajewsky, N., Rorsman, P., . (2004). A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432, 226-230 .10.1038/nature03076
[54] Rehmsmeier, M., Steffen, P., Hochsmann, M., and Giegerich, R. (2004). Fast and effective prediction of microRNA/target duplexes. RNA 10, 1507-1517 .
[55] Rusinov, V., Baev, V., Minkov, I.N., and Tabler, M. (2005). MicroInspector: a web tool for detection of miRNA binding sites in an RNA sequence. Nucleic Acids Res 33, W696-700 .10.1093/nar/gki364
[56] Saetrom, O., Sn?ve, O. Jr, and Saetrom, P. (2005). Weighted sequence motifs as an improved seeding step in microRNA target prediction algorithms. RNA 11, 995-1003 .
[57] Sarnow, P., Jopling, C.L., Norman, K.L., Schütz, S., and Wehner, K.A. (2006). MicroRNAs: expression, avoidance and subversion by vertebrate viruses. Nat Rev Microbiol 4, 651-659 .10.1038/nrmicro1473
[58] Selbach, M., Schwanh?usser, B., Thierfelder, N., Fang, Z., Khanin, R., and Rajewsky, N. (2008). Widespread changes in protein synthesis induced by microRNAs. Nature 455, 58-63 .10.1038/nature07228
[59] Sethupathy, P., Megraw, M., and Hatzigeorgiou, A.G. (2006). A guide through present computational approaches for the identification of mammalian microRNA targets. Nat Methods 3, 881-886 .10.1038/nmeth954
[60] Stark, A., Brennecke, J., Bushati, N., Russell, R.B., and Cohen, S.M. (2005). Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3’UTR evolution. Cell 123, 1133-1146 .
[61] Sturm, M., Hackenberg, M., Langenberger, D., and Frishman, D. (2010). TargetSpy: a supervised machine learning approach for microRNA target prediction. BMC Bioinformatics 11, 292.10.1186/1471-2105-11-292
[62] Trujillo, R.D., Yue, S.B., Tang, Y., O’Gorman, W.E., and Chen, C.Z. (2010). The potential functions of primary microRNAs in target recognition and repression. EMBO J 29, 3272-3285 .10.1038/emboj.2010.208
[63] Tsai, N.P., Lin, Y.L., and Wei, L.N. (2009). MicroRNA mir-346 targets the 5′-untranslated region of receptor-interacting protein 140 (RIP140) mRNA and up-regulates its protein expression. Biochem J 424, 411-418 .10.1042/BJ20090915
[64] Vinther, J., Hedegaard, M.M., Gardner, P.P., Andersen, J.S., and Arctander, P. (2006). Identification of miRNA targets with stable isotope labeling by amino acids in cell culture. Nucleic Acids Res 34, e107.10.1093/nar/gkl590
[65] Watanabe, Y., Tomita, M., and Kanai, A. (2007). Computational methods for microRNA target prediction. Methods Enzymol 427, 65-86 .10.1016/S0076-6879(07)27004-1
[66] Xiao, C., and Rajewsky, K. (2009). MicroRNA control in the immune system: basic principles. Cell 136, 26-36 .
[67] Zhang, L., Ding, L., Cheung, T.H., Dong, M.Q., Chen, J., Sewell, A.K., Liu, X., Yates, J.R. 3rd, and Han, M. (2007). Systematic identification of C. elegans miRISC proteins, miRNAs, and mRNA targets by their interactions with GW182 proteins AIN-1 and AIN-2. Mol Cell 28, 598-613 .10.1016/j.molcel.2007.09.014
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