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Genome-Wide RNA Secondary Structure Prediction

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RNA Structure Prediction

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2586))

Abstract

The information of RNA secondary structure has been widely applied to the inference of RNA function. However, a classical prediction method is not feasible to long RNAs such as mRNA due to the problems of computational time and numerical errors. To overcome those problems, sliding window methods have been applied while their results are not directly comparable to global RNA structure prediction. In this chapter, we introduce ParasoR, a method designed for parallel computation of genome-wide RNA secondary structures. To enable genome-wide prediction, ParasoR distributes dynamic programming (DP) matrices required for structure prediction to multiple computational nodes. Using the database of not the original DP variable but the ratio of variables, ParasoR can locally compute the structure scores such as stem probability or accessibility on demand. A comprehensive analysis of local secondary structures by ParasoR is expected to be a promising way to detect the statistical constraints on long RNAs.

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Change history

  • 05 April 2023

    A correction has been published.

References

  1. Kocak DD, Josephs EA, Bhandarkar V, Adkar SS, Kwon JB, Gersbach CA (2019) Increasing the specificity of CRISPR systems with engineered RNA secondary structures. Nat Biotechnol 37(6):657–666. https://doi.org/10.1038/s41587-019-0095-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mann M, Patrick RW, Backofen R (2017) IntaRNA 2.0: enhanced and customizable prediction of RNA-RNA interactions. Nucleic Acids Res 45(W1):W435–W439. https://doi.org/10.1093/nar/gkx279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mauger DM, Cabral BJ, Presnyak V, Su SV, Reid DW, Goodman B, Link K, Khatwani N, Reynders J, Moore MJ, McFadyen IJ (2019) mRNA structure regulates protein expression through changes in functional half-life. Proc Natl Acad Sci U S A 116(48):24075–24083. https://doi.org/10.1073/pnas.1908052116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ding Y, Tang Y, Kwok CK, Zhang Y, Bevilacqua PC, Assmann SM (2014) In vivo genome-wide profiling of RNA secondary structure reveals novel regulatory features. Nature 505(7485):696–700. https://doi.org/10.1038/nature12756

    Article  CAS  PubMed  Google Scholar 

  5. Michael Z, Stiegler P (1981) Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res. https://doi.org/10.1093/nar/9.1.133

  6. McCaskill JS (1990) The equilibrium partition function and base pair binding probabilities for RNA secondary structure. Biopolymers 29(6-7):1105–1119. https://doi.org/10.1002/bip.360290621

    Article  CAS  PubMed  Google Scholar 

  7. Elisabeth MM, Watson PY, Cottrell JW, Fedor MJ (2010) mRNA secondary structures fold sequentially but exchange rapidly in vivo. PLoS Biol 8(2):e1000307. https://doi.org/10.1371/journal.pbio.1000307

    Article  CAS  Google Scholar 

  8. Lange SJ, Maticzka D, Möhl M, Gagnon JN, Brown CM, Backofen R (2012) Global or local? Predicting secondary structure and accessibility in mRNAs. Nucleic Acids Res 40(12):5215–5226. https://doi.org/10.1093/nar/gks181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Turner DH, Mathews DH (2010) NNDB: the nearest neighbor parameter database for predicting stability of nucleic acid secondary structure. Nucleic Acids Res 38(Database issue):D280–D282. https://doi.org/10.1093/nar/gkp892

    Article  CAS  PubMed  Google Scholar 

  10. Andronescu M, Condon A, Hoos HH, Mathews DH, Murphy KP (2010) Computational approaches for RNA energy parameter estimation. RNA 16(12):2304–2318. https://doi.org/10.1261/rna.1950510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Do CB, Woods DA, Batzoglou S (2006) CONTRAfold: RNA secondary structure prediction without physics-based models. Bioinformatics 22(14):e90–e98. https://doi.org/10.1093/bioinformatics/btl246

    Article  CAS  PubMed  Google Scholar 

  12. Kiryu H, Kin T, Asai K (2008) Rfold: an exact algorithm for computing local base pairing probabilities. Bioinformatics 24(3):367–373. https://doi.org/10.1093/bioinformatics/btm591

    Article  CAS  PubMed  Google Scholar 

  13. Kiryu H, Terai G, Imamura O, Yoneyama H, Suzuki K, Asai K (2011) A detailed investigation of accessibilities around target sites of siRNAs and miRNAs. Bioinformatics 27(13):1788–1797. https://doi.org/10.1093/bioinformatics/btr276

    Article  CAS  PubMed  Google Scholar 

  14. Fukunaga T, Ozaki H, Terai G, Asai K, Iwasaki W, Kiryu H (2014) CapR: revealing structural specificities of RNA-binding protein target recognition using CLIP-seq data. Genome Biol 15(1):R16. https://doi.org/10.1186/gb-2014-15-1-r16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hamada M, Kiryu H, Sato K, Mituyama T, Asai K (2009) Prediction of RNA secondary structure using generalized centroid estimators. Bioinformatics 25(4):465–473. https://doi.org/10.1093/bioinformatics/btn601

    Article  CAS  PubMed  Google Scholar 

  16. Schroeder SJ (2009) Advances in RNA structure prediction from sequence: new tools for generating hypotheses about viral RNA structure-function relationships. J Virol 83(13):6326–6334. https://doi.org/10.1128/jvi.00251-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Puton T, Kozlowski LP, Rother KM (2014) CompaRNA: a server for continuous benchmarking of automated methods for RNA secondary structure prediction. Nucleic Acids Res 42(8):5403–5406. https://doi.org/10.1093/nar/gkt101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, Cheng JX, Murre C, Singh H, Glass CK (2010) Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. https://doi.org/10.1016/j.molcel.2010.05.004

  19. Alzner-DeWeerd B, Hecker LI, Barnett WE (1980) The nucleotide sequence of phenylalanine tRNA from the cytoplasm of Neurospora Crassa. Nucleic Acids Res. https://doi.org/10.1093/nar/8.5.1023

  20. Kawaguchi R, Kiryu H (2016) Parallel computation of genome-scale RNA secondary structure to detect structural constraints on human genome. BMC Bioinformatics 17(1):203. https://doi.org/10.1186/s12859-016-1067-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bernhart SH, Hofacker IL, Stadler PF (2006) Local RNA base pairing probabilities in large sequences. Bioinformatics 22(5):614–615. https://doi.org/10.1093/bioinformatics/btk014

    Article  CAS  PubMed  Google Scholar 

  22. Lorenz R, Bernhart SH, Höner Zu Siederdissen C, Tafer H, Flamm C, Stadler PF, Hofacker IL (2011) ViennaRNA package 2.0. Algorithms Mol Biol 6:26. https://doi.org/10.1186/1748-7188-6-26

    Article  PubMed  PubMed Central  Google Scholar 

  23. Pedersen JS, Bejerano G, Siepel A, Rosenbloom K, Lindblad-Toh K, Lander ES, Kent J, Miller W, Haussler D (2005) Identification and classification of conserved RNA secondary structures in the human genome. PLoS Comput Biol. https://doi.org/10.1371/journal.pcbi.0020033

  24. Will S, Joshi T, Hofacker IL, Stadler PF, Backofen R (2012) LocARNA-P: accurate boundary prediction and improved detection of structural RNAs. RNA 18(5):900–914. https://doi.org/10.1261/rna.029041.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Miladi M, Junge A, Costa F, Seemann SE, Havgaard JH, Gorodkin J, Backofen R (2017) RNAscClust: clustering RNA sequences using structure conservation and graph based Motifs. Bioinformatics 33(14):2089–2096. https://doi.org/10.1093/bioinformatics/btx114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gruber AR, Findeiß S, Washietl S, Hofacker IL, Stadler PF (2009) RNAz 2.0: improved noncoding RNA detection. Biocomputing 2010. https://doi.org/10.1142/9789814295291_0009

  27. Andrews RJ, Roche J, Moss WN (2018) ScanFold: an approach for genome-wide discovery of local RNA structural elements-applications to Zika virus and HIV. PeerJ 6:e6136. https://doi.org/10.7717/peerj.6136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Andrews RJ, Baber L, Moss WN (2017) RNAStructuromeDB: a genome-wide database for RNA structural inference. Sci Rep 7(1):17269. https://doi.org/10.1038/s41598-017-17510-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Thiel BC, Ochsenreiter R, Gadekar VP, Tanzer A, Hofacker IL (2018) RNA structure elements conserved between mouse and 59 other vertebrates. Genes 9(8):392. https://doi.org/10.3390/genes9080392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Danaee P, Rouches M, Wiley M, Dang D, Huang L, Hendrix D (2018) bpRNA: large-scale automated annotation and analysis of RNA secondary structure. Nucleic Acids Res 46(11):5381–5394. https://doi.org/10.1093/nar/gky285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Berkowitz ND, Silverman IM, Childress DM, Kazan H, Wang L, Gregory BD (2016) A comprehensive database of high-throughput sequencing-based RNA secondary structure probing data (Structure Surfer). BMC Bioinformatics 17(1):215. https://doi.org/10.1186/s12859-016-1071-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yesselman JD, Tian S, Liu X, Shi L, Li JB, Das R (2018) Updates to the RNA mapping Database (RMDB), version 2. Nucleic Acids Res 46(D1):D375–D379. https://doi.org/10.1093/nar/gkx873

    Article  CAS  PubMed  Google Scholar 

  33. Wirecki TK, Merdas K, Bernat A, Boniecki MJ, Bujnicki JM, Stefaniak F (2020) RNAProbe: a web server for normalization and analysis of RNA structure probing data. Nucleic Acids Res 48(W1):W292–W299. https://doi.org/10.1093/nar/gkaa396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Norris M, Kwok CK, Cheema J, Hartley M, Morris RJ, Aviran S, Ding Y (2017) FoldAtlas: a repository for genome-wide RNA structure probing data. Bioinformatics 33(2):306–308. https://doi.org/10.1093/bioinformatics/btw611

    Article  CAS  PubMed  Google Scholar 

  35. Zubradt M, Gupta P, Persad S, Lambowitz AM, Weissman JS, Rouskin S (2017) DMS-MaPseq for genome-wide or targeted RNA structure probing in vivo. Nat Methods 14(1):75–82. https://doi.org/10.1038/nmeth.4057

    Article  CAS  PubMed  Google Scholar 

  36. Liu B, Merriman DK, Choi SH, Schmacher MA, Plangger R, Kreutz C, Horner SM, Meyer KD, Al-Hashimi HM (2018) A potentially abundant junctional RNA motif stabilized by m6A and Mg2. Nat Commun 9(1):2761. https://doi.org/10.1038/s41467-018-05243-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Risa Karakida Kawaguchi .

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Kawaguchi, R.K., Kiryu, H. (2023). Genome-Wide RNA Secondary Structure Prediction. In: Kawaguchi, R.K., Iwakiri, J. (eds) RNA Structure Prediction. Methods in Molecular Biology, vol 2586. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2768-6_3

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  • DOI: https://doi.org/10.1007/978-1-0716-2768-6_3

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2767-9

  • Online ISBN: 978-1-0716-2768-6

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