Skip to main content

Genome-Wide Analysis of MicroRNA-Regulated Transcripts

  • Protocol
  • First Online:
Bioinformatics in MicroRNA Research

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1617))

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by either degrading transcripts or repressing translation . Over the past decade the significance of miRNAs has been unraveled by the characterization of their involvement in crucial cellular functions and the development of disease. However, continued progress in understanding the endogenous importance of miRNAs, as well as their potential uses as therapeutic tools, has been hindered by the difficulty of positively identifying miRNA targets. To face this challenge algorithmic approaches have primarily been utilized to date, but strictly mathematical models have thus far failed to produce a generally accurate, widely accepted methodology for accurate miRNA target determination. As such, several laboratory-based, comprehensive strategies for experimentally identifying all cellular miRNA regulations simultaneously have recently been developed. This chapter discusses the advantages and limitations of both classic and comprehensive strategies for miRNA target prediction .

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. 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(5):843–854

    Article  CAS  PubMed  Google Scholar 

  2. Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75(5):855–862

    Article  CAS  PubMed  Google Scholar 

  3. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403(6772):901–906. doi:10.1038/35002607

    Article  CAS  PubMed  Google Scholar 

  4. Moss EG, Lee RC, Ambros V (1997) The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell 88(5):637–646

    Article  CAS  PubMed  Google Scholar 

  5. Rhoades MW, Reinhart BJ, Lim LP, Burge CB, Bartel B, Bartel DP (2002) Prediction of plant microRNA targets. Cell 110(4):513–520

    Article  CAS  PubMed  Google Scholar 

  6. Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB (2003) Prediction of mammalian microRNA targets. Cell 115(7):787–798

    Article  CAS  PubMed  Google Scholar 

  7. Chi SW, Zang JB, Mele A, Darnell RB (2009) Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature 460(7254):479–486. doi:10.1038/nature08170

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233. doi:10.1016/j.cell.2009.01.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sethupathy P, Megraw M, Hatzigeorgiou AG (2006) A guide through present computational approaches for the identification of mammalian microRNA targets. Nat Methods 3(11):881–886. doi:10.1038/nmeth954

    Article  CAS  PubMed  Google Scholar 

  10. Alexiou P, Maragkakis M, Papadopoulos GL, Reczko M, Hatzigeorgiou AG (2009) Lost in translation: an assessment and perspective for computational microRNA target identification. Bioinformatics 25(23):3049–3055. doi:10.1093/bioinformatics/btp565

    Article  CAS  PubMed  Google Scholar 

  11. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N (2008) Widespread changes in protein synthesis induced by microRNAs. Nature 455(7209):58–63. doi:10.1038/nature07228

    Article  CAS  PubMed  Google Scholar 

  12. Kumar A, Wong AK, Tizard ML, Moore RJ, Lefevre C (2012) miRNA_Targets: a database for miRNA target predictions in coding and non-coding regions of mRNAs. Genomics 100(6):352–356. doi:10.1016/j.ygeno.2012.08.006

    Article  CAS  PubMed  Google Scholar 

  13. Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP (2008) The impact of microRNAs on protein output. Nature 455(7209):64–71. doi:10.1038/nature07242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Reyes-Herrera PH, Ficarra E, Acquaviva A, Macii E (2011) miREE: miRNA recognition elements ensemble. BMC Bioinformatics 12:454. doi:10.1186/1471–2105–12-454

    Article  PubMed  PubMed Central  Google Scholar 

  15. 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):769–773. doi:10.1038/nature03315

    Article  CAS  PubMed  Google Scholar 

  16. Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP (2007) MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 27(1):91–105. doi:10.1016/j.molcel.2007.06.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Linsley PS, Schelter J, Burchard J, Kibukawa M, Martin MM, Bartz SR, Johnson JM, Cummins JM, Raymond CK, Dai H, Chau N, Cleary M, Jackson AL, Carleton M, Lim L (2007) Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression. Mol Cell Biol 27(6):2240–2252. doi:10.1128/MCB.02005-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Vinther J, Hedegaard MM, Gardner PP, Andersen JS, Arctander P (2006) Identification of miRNA targets with stable isotope labeling by amino acids in cell culture. Nucleic Acids Res 34(16):e107. doi:10.1093/nar/gkl590

    Article  PubMed  PubMed Central  Google Scholar 

  19. Hobert O (2007) miRNAs play a tune. Cell 131(1):22–24. doi:10.1016/j.cell.2007.09.031

    Article  CAS  PubMed  Google Scholar 

  20. Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, Ha I, Baillie DL, Fire A, Ruvkun G, Mello CC (2001) Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106(1):23–34

    Article  CAS  PubMed  Google Scholar 

  21. Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD (2001) A cellular function for the RNA-interference enzyme dicer in the maturation of the let-7 small temporal RNA. Science 293(5531):834–838. doi:10.1126/science.1062961

    Article  CAS  PubMed  Google Scholar 

  22. Ketting RF, Fischer SE, Bernstein E, Sijen T, Hannon GJ, Plasterk RH (2001) Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 15(20):2654–2659. doi:10.1101/gad.927801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Knight SW, Bass BL (2001) A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science 293(5538):2269–2271. doi:10.1126/science.1062039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nakamoto M, Jin P, O'Donnell WT, Warren ST (2005) Physiological identification of human transcripts translationally regulated by a specific microRNA. Hum Mol Genet 14(24):3813–3821. doi:10.1093/hmg/ddi397

    Article  CAS  PubMed  Google Scholar 

  25. Easow G, Teleman AA, Cohen SM (2007) Isolation of microRNA targets by miRNP immunopurification. RNA 13(8):1198–1204. doi:10.1261/rna.563707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438(7068):685–689. doi:10.1038/nature04303

    Article  PubMed  Google Scholar 

  27. Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA, Vetrie D, Okkenhaug K, Enright AJ, Dougan G, Turner M, Bradley A (2007) Requirement of bic/microRNA-155 for normal immune function. Science 316(5824):608–611. doi:10.1126/science.1139253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Orom UA, Kauppinen S, Lund AH (2006) LNA-modified oligonucleotides mediate specific inhibition of microRNA function. Gene 372:137–141. doi:10.1016/j.gene.2005.12.031

    Article  CAS  PubMed  Google Scholar 

  29. Ebert MS, Neilson JR, Sharp PA (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4(9):721–726. doi:10.1038/nmeth1079

    Article  CAS  PubMed  Google Scholar 

  30. Thomas JR, Hergenrother PJ (2008) Targeting RNA with small molecules. Chem Rev 108(4):1171–1224. doi:10.1021/cr0681546

    Article  CAS  PubMed  Google Scholar 

  31. Zhang S, Chen L, Jung EJ, Calin GA (2010) Targeting microRNAs with small molecules: from dream to reality. Clin Pharmacol Ther 87(6):754–758. doi:10.1038/clpt.2010.46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hendrickson DG, Hogan DJ, McCullough HL, Myers JW, Herschlag D, Ferrell JE, Brown PO (2009) Concordant regulation of translation and mRNA abundance for hundreds of targets of a human microRNA. PLoS Biol 7(11):e1000238. doi:10.1371/journal.pbio.1000238

    Article  PubMed  PubMed Central  Google Scholar 

  33. Guo H, Ingolia NT, Weissman JS, Bartel DP (2010) Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466(7308):835–840. doi:10.1038/nature09267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, Mann M (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1(5):376–386

    Article  CAS  PubMed  Google Scholar 

  35. Zhu H, Pan S, Gu S, Bradbury EM, Chen X (2002) Amino acid residue specific stable isotope labeling for quantitative proteomics. Rapid Commun Mass Spectrom 16(22):2115–2123. doi:10.1002/rcm.831

    Article  CAS  PubMed  Google Scholar 

  36. Zhu S, Si ML, Wu H, Mo YY (2007) MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 282(19):14328–14336. doi:10.1074/jbc.M611393200

    Article  CAS  PubMed  Google Scholar 

  37. Muniyappa MK, Dowling P, Henry M, Meleady P, Doolan P, Gammell P, Clynes M, Barron N (2009) MiRNA-29a regulates the expression of numerous proteins and reduces the invasiveness and proliferation of human carcinoma cell lines. Eur J Cancer 45(17):3104–3118. doi:10.1016/j.ejca.2009.09.014

    Article  CAS  PubMed  Google Scholar 

  38. Tenenbaum SA, Carson CC, Lager PJ, Keene JD (2000) Identifying mRNA subsets in messenger ribonucleoprotein complexes by using cDNA arrays. Proc Natl Acad Sci U S A 97(26):14085–14090. doi:10.1073/pnas.97.26.14085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Meier J, Hovestadt V, Zapatka M, Pscherer A, Lichter P, Seiffert M (2013) Genome-wide identification of translationally inhibited and degraded miR-155 targets using RNA-interacting protein-IP. RNA Biol 10(6):1018–1029. doi:10.4161/rna.24553

    Article  PubMed  Google Scholar 

  40. Beitzinger M, Peters L, Zhu JY, Kremmer E, Meister G (2007) Identification of human microRNA targets from isolated argonaute protein complexes. RNA Biol 4(2):76–84

    Article  CAS  PubMed  Google Scholar 

  41. Karginov FV, Conaco C, Xuan Z, Schmidt BH, Parker JS, Mandel G, Hannon GJ (2007) A biochemical approach to identifying microRNA targets. Proc Natl Acad Sci U S A 104(49):19291–19296. doi:10.1073/pnas.0709971104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hendrickson DG, Hogan DJ, Herschlag D, Ferrell JE, Brown PO (2008) Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. PLoS One 3(5):e2126. doi:10.1371/journal.pone.0002126

    Article  PubMed  PubMed Central  Google Scholar 

  43. Zhang L, Ding L, Cheung TH, Dong MQ, Chen J, Sewell AK, Liu X, Yates JR 3rd, 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(4):598–613. doi:10.1016/j.molcel.2007.09.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mili S, Steitz JA (2004) Evidence for reassociation of RNA-binding proteins after cell lysis: implications for the interpretation of immunoprecipitation analyses. RNA 10(11):1692–1694. doi:10.1261/rna.7151404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ule J, Jensen KB, Ruggiu M, Mele A, Ule A, Darnell RB (2003) CLIP identifies Nova-regulated RNA networks in the brain. Science 302(5648):1212–1215. doi:10.1126/science.1090095

    Article  CAS  PubMed  Google Scholar 

  46. Zisoulis DG, Lovci MT, Wilbert ML, Hutt KR, Liang TY, Pasquinelli AE, Yeo GW (2010) Comprehensive discovery of endogenous argonaute binding sites in Caenorhabditis elegans. Nat Struct Mol Biol 17(2):173–179. doi:10.1038/nsmb.1745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zhang C, Darnell RB (2011) Mapping in vivo protein-RNA interactions at single-nucleotide resolution from HITS-CLIP data. Nat Biotechnol 29(7):607–614. doi:10.1038/nbt.1873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, Rothballer A, Ascano M Jr, Jungkamp AC, Munschauer M, Ulrich A, Wardle GS, Dewell S, Zavolan M, Tuschl T (2010a) Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141(1):129–141. doi:10.1016/j.cell.2010.03.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, Rothballer A, Ascano M, Jungkamp AC, Munschauer M, Ulrich A, Wardle GS, Dewell S, Zavolan M, Tuschl T (2010b) PAR-CliP--a method to identify transcriptome-wide the binding sites of RNA binding proteins. J Vis Exp 41:2034. doi:10.3791/2034

    Google Scholar 

  50. Kishore S, Jaskiewicz L, Burger L, Hausser J, Khorshid M, Zavolan M (2011) A quantitative analysis of CLIP methods for identifying binding sites of RNA-binding proteins. Nat Methods 8(7):559–564. doi:10.1038/nmeth.1608

    Article  CAS  PubMed  Google Scholar 

  51. Konig J, Zarnack K, Rot G, Curk T, Kayikci M, Zupan B, Turner DJ, Luscombe NM, Ule J (2011) iCLIP—transcriptome-wide mapping of protein-RNA interactions with individual nucleotide resolution. J Vis Exp 50:2638. doi:10.3791/2638

    Google Scholar 

  52. Broughton JP, Pasquinelli AE (2013) Identifying argonaute binding sites in Caenorhabditis elegans using iCLIP. Methods 63(2):119–125. doi:10.1016/j.ymeth.2013.03.033

    Article  CAS  PubMed Central  Google Scholar 

  53. Helwak A, Kudla G, Dudnakova T, Tollervey D (2013) Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell 153(3):654–665. doi:10.1016/j.cell.2013.03.043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Travis AJ, Moody J, Helwak A, Tollervey D, Kudla G (2014) Hyb: a bioinformatics pipeline for the analysis of CLASH (crosslinking, ligation and sequencing of hybrids) data. Methods 65(3):263–273. doi:10.1016/j.ymeth.2013.10.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Gregory BD, O’Malley RC, Lister R, Urich MA, Tonti-Filippini J, Chen H, Millar AH, Ecker JR (2008) A link between RNA metabolism and silencing affecting Arabidopsis development. Dev Cell 14(6):854–866. doi:10.1016/j.devcel.2008.04.005

    Article  CAS  PubMed  Google Scholar 

  56. Addo-Quaye C, Miller W, Axtell MJ (2009) CleaveLand: a pipeline for using degradome data to find cleaved small RNA targets. Bioinformatics 25(1):130–131. doi:10.1093/bioinformatics/btn604

    Article  CAS  PubMed  Google Scholar 

  57. German MA, Luo S, Schroth G, Meyers BC, Green PJ (2009) Construction of parallel analysis of RNA ends (PARE) libraries for the study of cleaved miRNA targets and the RNA degradome. Nat Protoc 4(3):356–362. doi:10.1038/nprot.2009.8

    Article  CAS  PubMed  Google Scholar 

  58. German MA, Pillay M, Jeong DH, Hetawal A, Luo S, Janardhanan P, Kannan V, Rymarquis LA, Nobuta K, German R, De Paoli E, Lu C, Schroth G, Meyers BC, Green PJ (2008) Global identification of microRNA-target RNA pairs by parallel analysis of RNA ends. Nat Biotechnol 26(8):941–946. doi:10.1038/nbt1417

    Article  CAS  PubMed  Google Scholar 

  59. Li YF, Zheng Y, Addo-Quaye C, Zhang L, Saini A, Jagadeeswaran G, Axtell MJ, Zhang W, Sunkar R (2010) Transcriptome-wide identification of microRNA targets in rice. Plant J 62(5):742–759. doi:10.1111/j.1365-313X.2010.04187.x

    Article  CAS  PubMed  Google Scholar 

  60. Bracken CP, Szubert JM, Mercer TR, Dinger ME, Thomson DW, Mattick JS, Michael MZ, Goodall GJ (2011) Global analysis of the mammalian RNA degradome reveals widespread miRNA-dependent and miRNA-independent endonucleolytic cleavage. Nucleic Acids Res 39(13):5658–5668. doi:10.1093/nar/gkr110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Karginov FV, Cheloufi S, Chong MM, Stark A, Smith AD, Hannon GJ (2010) Diverse endonucleolytic cleavage sites in the mammalian transcriptome depend upon microRNAs, Drosha, and additional nucleases. Mol Cell 38(6):781–788. doi:10.1016/j.molcel.2010.06.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Shin C, Nam JW, Farh KK, Chiang HR, Shkumatava A, Bartel DP (2010) Expanding the microRNA targeting code: functional sites with centered pairing. Mol Cell 38(6):789–802. doi:10.1016/j.molcel.2010.06.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Eckardt NA (2009) Investigating translational repression by microRNAs in Arabidopsis. Plant Cell 21(6):1624. doi:10.1105/tpc.109.210613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Chiu HS, Llobet-Navas D, Yang X, Chung WJ, Ambesi-Impiombato A, Iyer A, Kim HR, Seviour EG, Luo Z, Sehgal V, Moss T, Lu Y, Ram P, Silva J, Mills GB, Califano A, Sumazin P (2015) Cupid: simultaneous reconstruction of microRNA-target and ceRNA networks. Genome Res 25(2):257–267. doi:10.1101/gr.178194.114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Maragkakis M, Reczko M, Simossis VA, Alexiou P, Papadopoulos GL, Dalamagas T, Giannopoulos G, Goumas G, Koukis E, Kourtis K, Vergoulis T, Koziris N, Sellis T, Tsanakas P, Hatzigeorgiou AG (2009) DIANA-microT web server: elucidating microRNA functions through target prediction. Nucleic Acids Res 37(Web Server issue):W273–W276. doi:10.1093/nar/gkp292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Maragkakis M, Vergoulis T, Alexiou P, Reczko M, Plomaritou K, Gousis M, Kourtis K, Koziris N, Dalamagas T, Hatzigeorgiou AG (2011) DIANA-microT Web server upgrade supports Fly and Worm miRNA target prediction and bibliographic miRNA to disease association. Nucleic Acids Res 39(Web Server issue):W145–W148. doi:10.1093/nar/gkr294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Paraskevopoulou MD, Georgakilas G, Kostoulas N, Vlachos IS, Vergoulis T, Reczko M, Filippidis C, Dalamagas T, Hatzigeorgiou AG (2013) DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows. Nucleic Acids Res 41(Web Server issue):W169–W173. doi:10.1093/nar/gkt393

    Article  PubMed  PubMed Central  Google Scholar 

  68. Gaidatzis D, van Nimwegen E, Hausser J, Zavolan M (2007) Inference of miRNA targets using evolutionary conservation and pathway analysis. BMC Bioinformatics 8:69. doi:10.1186/1471-2105-8-69

    Article  PubMed  PubMed Central  Google Scholar 

  69. Ahmadi H, Ahmadi A, Azimzadeh-Jamalkandi S, Shoorehdeli MA, Salehzadeh-Yazdi A, Bidkhori G, Masoudi-Nejad A (2013) HomoTarget: a new algorithm for prediction of microRNA targets in Homo sapiens. Genomics 101(2):94–100. doi:10.1016/j.ygeno.2012.11.005

    Article  CAS  PubMed  Google Scholar 

  70. Sales G, Coppe A, Bisognin A, Biasiolo M, Bortoluzzi S, Romualdi C (2010) MAGIA, a web-based tool for miRNA and genes integrated analysis. Nucleic Acids Res 38(Web Server issue):W352–W359. doi:10.1093/nar/gkq423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS (2003) MicroRNA targets in drosophila. Genome Biol 5(1):R1. doi:10.1186/gb-2003-5-1-r1

    Article  PubMed  PubMed Central  Google Scholar 

  72. Hsu JB, Chiu CM, Hsu SD, Huang WY, Chien CH, Lee TY, Huang HD (2011) miRTar: an integrated system for identifying miRNA-target interactions in human. BMC Bioinformatics 12:300. doi:10.1186/1471–2105–12-300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N (2005) Combinatorial microRNA target predictions. Nat Genet 37(5):495–500. doi:10.1038/ng1536

    Article  CAS  PubMed  Google Scholar 

  74. Kertesz M, Iovino N, Unnerstall U, Gaul U, Segal E (2007) The role of site accessibility in microRNA target recognition. Nat Genet 39(10):1278–1284. doi:10.1038/ng2135

    Article  CAS  PubMed  Google Scholar 

  75. Dai X, Zhao PX (2011) psRNATarget: a plant small RNA target analysis server. Nucleic Acids Res 39(Web Server issue):W155–W159. doi:10.1093/nar/gkr319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R (2004) Fast and effective prediction of microRNA/target duplexes. RNA 10(10):1507–1517. doi:10.1261/rna.5248604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. 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(1):15–20. doi:10.1016/j.cell.2004.12.035

    Article  CAS  PubMed  Google Scholar 

  78. Friedman RC, Farh KK, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19(1):92–105. doi:10.1101/gr.082701.108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Garcia DM, Baek D, Shin C, Bell GW, Grimson A, Bartel DP (2011) Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs. Nat Struct Mol Biol 18(10):1139–1146. doi:10.1038/nsmb.2115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Agarwal V, Bell GW, Nam JW, Bartel DP (2015) Predicting effective microRNA target sites in mammalian mRNAs. eLife 4:e05005. doi:10.7554/eLife.05005

    Article  PubMed Central  Google Scholar 

  81. Huang JC, Babak T, Corson TW, Chua G, Khan S, Gallie BL, Hughes TR, Blencowe BJ, Frey BJ, Morris QD (2007) Using expression profiling data to identify human microRNA targets. Nat Methods 4(12):1045–1049. doi:10.1038/nmeth1130

    Article  CAS  PubMed  Google Scholar 

  82. Bandyopadhyay S, Ghosh D, Mitra R, Zhao Z (2015) MBSTAR: multiple instance learning for predicting specific functional binding sites in microRNA targets. Sci Rep 5:8004. doi:10.1038/srep08004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Thadani R, Tammi MT (2006) MicroTar: predicting microRNA targets from RNA duplexes. BMC Bioinformatics 7(Suppl 5):S20. doi:10.1186/1471-2105-7-S5-S20

    Article  PubMed  PubMed Central  Google Scholar 

  84. Wang X, El Naqa IM (2008) Prediction of both conserved and nonconserved microRNA targets in animals. Bioinformatics 24(3):325–332. doi:10.1093/bioinformatics/btm595

    Article  PubMed  Google Scholar 

  85. Hammell M, Long D, Zhang L, Lee A, Carmack CS, Han M, Ding Y, Ambros V (2008) mirWIP: microRNA target prediction based on microRNA-containing ribonucleoprotein-enriched transcripts. Nat Methods 5(9):813–819. doi:10.1038/nmeth.1247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Friedman Y, Karsenty S, Linial M (2014) miRror-suite: decoding coordinated regulation by microRNAs. Database (Oxford) 2014:bau043. doi:10.1093/database/bau043

    Article  Google Scholar 

  87. Friedman Y, Naamati G, Linial M (2010) MiRror: a combinatorial analysis web tool for ensembles of microRNAs and their targets. Bioinformatics 26(15):1920–1921. doi:10.1093/bioinformatics/btq298

    Article  CAS  PubMed  Google Scholar 

  88. Yang Y, Wang YP, Li KB (2008) MiRTif: a support vector machine-based microRNA target interaction filter. BMC Bioinformatics 9(Suppl 12):S4. doi:10.1186/1471-2105-9-S12-S4

    Article  PubMed  PubMed Central  Google Scholar 

  89. Yousef M, Jung S, Kossenkov AV, Showe LC, Showe MK (2007) Naive Bayes for microRNA target predictions--machine learning for microRNA targets. Bioinformatics 23(22):2987–2992. doi:10.1093/bioinformatics/btm484

    Article  CAS  PubMed  Google Scholar 

  90. Uren PJ, Bahrami-Samani E, Burns SC, Qiao M, Karginov FV, Hodges E, Hannon GJ, Sanford JR, Penalva LO, Smith AD (2012) Site identification in high-throughput RNA-protein interaction data. Bioinformatics 28(23):3013–3020. doi:10.1093/bioinformatics/bts569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. van Dongen S, Abreu-Goodger C, Enright AJ (2008) Detecting microRNA binding and siRNA off-target effects from expression data. Nat Methods 5(12):1023–1025. doi:10.1038/nmeth.1267

    Article  PubMed  PubMed Central  Google Scholar 

  92. Coronnello C, Benos PV (2013) ComiR: Combinatorial microRNA target prediction tool. Nucleic Acids Res 41(Web Server issue):W159–W164. doi:10.1093/nar/gkt379

    Article  PubMed  PubMed Central  Google Scholar 

  93. Betel D, Koppal A, Agius P, Sander C, Leslie C (2010) Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol 11(8):R90. doi:10.1186/gb-2010-11-8-r90

    Article  PubMed  PubMed Central  Google Scholar 

  94. Bandyopadhyay S, Mitra R (2009) TargetMiner: microRNA target prediction with systematic identification of tissue-specific negative examples. Bioinformatics 25(20):2625–2631. doi:10.1093/bioinformatics/btp503

    Article  CAS  PubMed  Google Scholar 

  95. Chandra V, Girijadevi R, Nair AS, Pillai SS, Pillai RM (2010) MTar: a computational microRNA target prediction architecture for human transcriptome. BMC Bioinformatics 11(Suppl 1):S2. doi:10.1186/1471-2105-11-S1-S2

    Article  PubMed  PubMed Central  Google Scholar 

  96. Chang TH, Huang HY, Hsu JB, Weng SL, Horng JT, Huang HD (2013) An enhanced computational platform for investigating the roles of regulatory RNA and for identifying functional RNA motifs. BMC Bioinformatics 14(Suppl 2):S4. doi:10.1186/1471–2105-14-S2-S4

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Glen M. Borchert Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media LLC

About this protocol

Cite this protocol

Chevalier, D., Borchert, G.M. (2017). Genome-Wide Analysis of MicroRNA-Regulated Transcripts. In: Huang, J., et al. Bioinformatics in MicroRNA Research. Methods in Molecular Biology, vol 1617. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7046-9_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7046-9_7

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7044-5

  • Online ISBN: 978-1-4939-7046-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics