Skip to main content

STarMir Tools for Prediction of microRNA Binding Sites

  • Protocol
  • First Online:
RNA Structure Determination

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1490))

Abstract

MicroRNAs (miRNAs) are a class of endogenous short noncoding RNAs that regulate gene expression by targeting messenger RNAs (mRNAs), which results in translational repression and/or mRNA degradation. As regulatory molecules, miRNAs are involved in many mammalian biological processes and also in the manifestation of certain human diseases. As miRNAs play central role in the regulation of gene expression, understanding miRNA-binding patterns is essential to gain an insight of miRNA mediated gene regulation and also holds promise for therapeutic applications. Computational prediction of miRNA binding sites on target mRNAs facilitates experimental investigation of miRNA functions. This chapter provides protocols for using the STarMir web server for improved predictions of miRNA binding sites on a target mRNA. As an application module of the Sfold RNA package, the current version of STarMir is an implementation of logistic prediction models developed with high-throughput miRNA binding data from cross-linking immunoprecipitation (CLIP) studies. The models incorporated comprehensive thermodynamic, structural, and sequence features, and were found to make improved predictions of both seed and seedless sites, in comparison to the established algorithms (Liu et al., Nucleic Acids Res 41:e138, 2013). Their broad applicability was indicated by their good performance in cross-species validation. STarMir is freely available at http://sfold.wadsworth.org/starmir.html.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
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

References

  1. Liu C, Mallick B, Long D, Rennie WA, Wolenc A, Carmack CS, Ding Y (2013) CLIP-based prediction of mammalian microRNA binding sites. Nucleic Acids Res 41:e138. doi:10.1093/nar/gkt435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ambros V (2004) The functions of animal microRNAs. Nature 431(7006):350–355. doi:10.1038/nature02871

    Article  CAS  PubMed  Google Scholar 

  3. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297

    Article  CAS  PubMed  Google Scholar 

  4. 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 

  5. Harfe BD (2005) MicroRNAs in vertebrate development. Curr Opin Genet Dev 15(4):410–415. doi:10.1016/j.gde.2005.06.012

    Article  CAS  PubMed  Google Scholar 

  6. Esau CC, Monia BP (2007) Therapeutic potential for microRNAs. Adv Drug Deliv Rev 59(2-3):1–114. doi:10.1016/j.addr.2007.03.007

    Article  Google Scholar 

  7. Erson AE, Petty EM (2008) MicroRNAs in development and disease. Clin Genet 74(4):296–306. doi:10.1111/j.1399-0004.2008.01076.x

    Article  CAS  PubMed  Google Scholar 

  8. 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 

  9. 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 

  10. 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 

  11. Tay Y, Zhang J, Thomson AM, Lim B, Rigoutsos I (2008) MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455(7216):1124–1128.doi:10.1038/nature07299

    Article  CAS  PubMed  Google Scholar 

  12. Vella MC, Choi EY, Lin SY, Reinert K, Slack FJ (2004) The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from the lin-41 3′UTR. In: Genes Dev 18(2):132–137. doi:10.1101/gad.1165404

    CAS  Google Scholar 

  13. Didiano D, Hobert O (2006) Perfect seed pairing is not a generally reliable predictor for miRNA-target interactions. Nat Struct Mol Biol 13(9):849–851. doi:10.1038/nsmb1138

    Article  CAS  PubMed  Google Scholar 

  14. Loeb GB, Khan AA, Canner D, Hiatt JB, Shendure J, Darnell RB, Leslie CS, Rudensky AY (2012) Transcriptome-wide miR-155 binding map reveals widespread noncanonical microRNA targeting. Mol Cell 48(5):760–770. doi:10.1016/j.molcel.2012.10.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lal A, Navarro F, Maher CA, Maliszewski LE, Yan N, O’Day E, Chowdhury D, Dykxhoorn DM, Tsai P, Hofmann O, Becker KG, Gorospe M, Hide W, Lieberman J (2009) 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 35(5):610–625. doi:10.1016/j.molcel.2009.08.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. 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 

  17. Ding Y, Lawrence CE (2003) A statistical sampling algorithm for RNA secondary structure prediction. Nucleic Acids Res 31(24):7280–7301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ding Y, Chan CY, Lawrence CE (2004) Sfold web server for statistical folding and rational design of nucleic acids. Nucleic Acids Res 32(Web Server issue):W135–W141. doi:10.1093/nar/gkh449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Long D, Lee R, Williams P, Chan CY, Ambros V, Ding Y (2007) Potent effect of target structure on microRNA function. Nat Struct Mol Biol 14(4):287–294. doi:10.1038/nsmb1226

    Article  CAS  PubMed  Google Scholar 

  20. Long D, Chan CY, Ding Y (2008) Analysis of microRNA-target interactions by a target structure based hybridization model. Pac Symp Biocomput:64–74

    Google Scholar 

  21. 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 

  22. Liu C, Rennie WA, Mallick B, Kanoria S, Long D, Wolenc A, Carmack CS, Ding Y (2014) MicroRNA binding sites in C. elegans 3′ UTRs. RNA Biol 11(6):693–701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Malhas A, Saunders NJ, Vaux DJ (2010) The nuclear envelope can control gene expression and cell cycle progression via miRNA regulation. Cell Cycle 9(3):531–539

    Article  CAS  PubMed  Google Scholar 

  24. Liu C, Rennie WA, Carmack CS, Kanoria S, Cheng J, Lu J, Ding Y (2014) Effects of genetic variations on microRNA: target interactions. Nucleic Acids Res 42(15):9543–9552. doi:10.1093/nar/gku675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 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 

  26. 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 (2010) 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 

  27. 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 

  28. 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 

  29. Rennie W, Liu C, Carmack CS, Wolenc A, Kanoria S, Lu J, Long D, Ding Y (2014) STarMir: a web server for prediction of microRNA binding sites. Nucleic Acids Res 42(Web Server issue):W114–W118. doi:10.1093/nar/gku376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kozomara A, Griffiths-Jones S (2014) miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 42(Database issue):D68–D73. doi:10.1093/nar/gkt1181

    Article  CAS  PubMed  Google Scholar 

  31. Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier LW, Richards S, Weinstock GM, Wilson RK, Gibbs RA, Kent WJ, Miller W, Haussler D (2005) Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res 15(8):1034–1050. doi:10.1101/gr.3715005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The Computational Molecular Biology and Statistics Core at the Wadsworth Center is acknowledged for supporting computing resources for this work. This work is supported in part by the National Science Foundation (DBI-0650991 to Y.D.), National Institutes of Health (GM099811, GM116885 to Y.D. and J.L.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ye Ding .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Kanoria, S., Rennie, W., Liu, C., Carmack, C.S., Lu, J., Ding, Y. (2016). STarMir Tools for Prediction of microRNA Binding Sites. In: Turner, D., Mathews, D. (eds) RNA Structure Determination. Methods in Molecular Biology, vol 1490. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6433-8_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-6433-8_6

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6431-4

  • Online ISBN: 978-1-4939-6433-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics