RNA snp: Efficient Detection of Local RNA Secondary Structure Changes Induced by SNP s

Abstract

Structural characteristics are essential for the functioning of many noncoding RNAs and cis-regulatory elements of mRNAs. SNPs may disrupt these structures, interfere with their molecular function, and hence cause a phenotypic effect. RNA folding algorithms can provide detailed insights into structural effects of SNPs. The global measures employed so far suffer from limited accuracy of folding programs on large RNAs and are computationally too demanding for genome-wide applications. Here, we present a strategy that focuses on the local regions of maximal structural change between mutant and wild-type. These local regions are approximated in a "screening mode" that is intended for genome-wide applications. Furthermore, localized regions are identified as those with maximal discrepancy. The mutation effects are quantified in terms of empirical P values. To this end, the RNAsnp software uses extensive precomputed tables of the distribution of SNP effects as function of length and GC content. RNAsnp thus achieves both a noise reduction and speed-up of several orders of magnitude over shuffling-based approaches. On a data set comprising 501 SNPs associated with human-inherited diseases, we predict 54 to have significant local structural effect in the untranslated region of mRNAs.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 73

1. 1.

   Abbink TEM, Berkhout B. RNA structure modulates splicing efficiency at the Human Immunodeficiency Virus type 1 major splice donor. J Virol. 2008;82:3090-3098.

   Not in our library10.1128/jvi.01479-07

2. 2.

   Bahadur RP, Zacharias M, Janin J. Dissecting protein–RNA recognition sites. Nucleic Acids Res. 2008;36:2705-2716.

   Not in our library10.1093/nar/gkn102

3. 3.

   Barash D. Deleterious mutation prediction in the secondary structure of RNAs. Nucleic Acids Res. 2003;31:6578-6584.

   Not in our library10.1093/nar/gkg872

4. 4.

   Bartoszewski RA, Jablonsky M, Bartoszewska S, Stevenson L, Dai Q, Kappes J, Collawn JF, Bebok Z. A synonymous single nucleotide polymorphism in DeltaF508 CFTR alters the secondary structure of the mRNA and the expression of the mutant protein. J Biol Chem. 2010;285:28741-28748.

   Not in our library10.1074/jbc.m110.154575

5. 5.

   Bernhart S, Hofacker IL, Stadler PF. Local RNA base pairing probabilities in large sequences. Bioinformatics. 2006;22:614-615.

   Not in our library10.1093/bioinformatics/btk014

6. 6.

   Bonhoeffer S, McCaskill JS, Stadler PF, Schuster P. RNA multi-structure landscapes. A study based on temperature dependent partition functions. Eur Biophys J. 1993;22:13-24.

   Not in our library10.1007/bf00205808

7. 7.

   Cao J, Schneeberger K, Ossowski S, Günther T, Bender S, Fitz J, Koenig D, Lanz C, Stegle O, Lippert C, Wang X, Ott F, Müller J, Alonso-Blanco C, Borgwardt K, Schmid KJ, Weigel D. Whole-genome sequencing of multiple Arabidopsis thaliana populations. Nat Genet. 2011;43:956-963.

   Not in our library10.1038/ng.911

8. 8.

   Chatterjee S, Pal JK. Role of 5′- and 3′-untranslated regions of mRNAs in human diseases. Biol Cell. 2009;101:251-262.

   Not in our library10.1042/bc20080104

9. 9.

   Chen JM, Férec C, Cooper DN. A systematic analysis of disease-associated variants in the 3′ regulatory regions of human protein-coding genes II: the importance of mRNA secondary structure in assessing the functionality of 3′ UTR variants. Hum Genet. 2006;120:301-333.

   Not in our library10.1007/s00439-006-0218-x

10. 10.

    Churkin A, Barash D. RNAmute: RNA secondary structure mutation analysis tool. BMC Bioinform. 2006;7:221.

    Not in our library10.1186/1471-2105-7-221

11. 11.

    Coles S. An introduction to statistical modeling of extreme values. 2001.

    Not in our library

12. 12.

    Dalli D, Wilm A, Mainz I, Steger G. STRAL: progressive alignment of non-coding RNA using base pairing probability vectors in quadratic time. Bioinformatics. 2006;22:1593-1599.

    Not in our library10.1093/bioinformatics/btl142

13. 13.

    Dotú I, Lorenz WA, Van Hentenryck P, Clote P. RNA structural segmentation. Pac Symp Biocomput. 2010;15:57-68.

    Not in our library10.1142/9789814295291_0008

14. 14.

    Duan J, Wainwright MS, Comeron JM, Saitou N, Sanders AR, Gelernter J, Gejman PV. Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA, stability and synthesis of the receptor. Hum Mol Genet. 2003;12:205-216.

    Not in our library10.1093/hmg/ddg055

15. 15.

    Fontana W, Konings DAM, Stadler PF, Schuster P. Statistics of RNA secondary structures. Biopolymers. 1993;33:1389-1404.

    Not in our library10.1002/bip.360330909

16. 16.

    Gardner PP, Daub J, Tate J, Moore BL, Osuch IH, Griffiths-Jones S, Finn RD, Nawrocki EP, Kolbe DL, Eddy SR, Bateman A. Rfam: Wikipedia, clans and the “decimal” release. Nucleic Acids Res. 2011;39:D141-D151.

    Not in our library10.1093/nar/gkq1129

17. 17.

    Gesell T, Washietl S. Dinucleotide controlled null models for comparative RNA gene prediction. BMC Bioinform. 2008;9:248.

    Not in our library10.1186/1471-2105-9-248

18. 18.

    Glinskii AB, Ma J, Ma S, Grant D, Lim CU, Sell S, Glinsky G. Identification of intergenic trans-regulatory RNAs containing a disease-linked SNP sequence and targeting cell cycle progression/differentiation pathways in multiple common human disorders. Cell Cycle. 2009;8:3925-3942.

    Not in our library10.4161/cc.8.23.10113

19. 19.

    Gong J, Tong Y, Zhang HM, Wang K, Hu T, Shan G, Sun J, Guo AY. Genome-wide identification of SNPs in microRNA genes and the SNP effects on microRNA target binding and biogenesis. Hum Mutat. 2012;33:254-263.

    Not in our library10.1002/humu.21641

20. 20.

    Gorodkin J, Hofacker IL, Torarinsson E, Yao Z, Havgaard JH, Ruzzo WL. De novo prediction of structured RNAs from genomic sequences. Trends Biotechnol. 2010;28:9-19.

    Not in our library10.1016/j.tibtech.2009.09.006

21. 21.

    Grover R, Sharathchandra A, Ponnuswamy A, Khan D, Das S. Effect of mutations on the p53 IRESRNA structure: implications for de-regulation of the synthesis of p53 isoforms. RNA Biol. 2011;8:132-142.

    Not in our library10.4161/rna.8.1.14260

22. 22.

    Gruber AR, Findeiß S, Washietl S, Hofacker IL, Stadler PF. RNAz 2.0: improved noncoding RNA detection. Pac Symp Biocomput. 2010;15:69-79.

    Not in our library

23. 23.
    Disease-Associated Mutations That Alter the RNA Structural Ensemble · 2010

    No notice
24. 24.

    Hariharan M, Scaria V, Brahmachari SK. dbSMR: a novel resource of genome-wide SNPs affecting microRNA mediated regulation. BMC Bioinform. 2009;10:108.

    Not in our library10.1186/1471-2105-10-108

25. 25.

    Hill MJ, Reynolds GP. Functional consequences of two HTR2C polymorphisms associated with antipsychotic-induced weight gain. Pharmacogenomics. 2011;5:1-8.

    Not in our library10.2217/pgs.11.16

26. 26.

    Hofacker IL, Bernhart SHF, Stadler PF. Alignment of RNA base pairing probability matrices. Bioinformatics. 2004;20:2222-2227.

    Not in our library10.1093/bioinformatics/bth229

27. 27.

    Hofacker IL, Fekete M, Stadler PF. Secondary structure prediction for aligned RNA sequences. J Mol Biol. 2002;319:1059-1066.

    Not in our library10.1016/s0022-2836(02)00308-x

28. 28.

    Hofacker IL, Fontana W, Stadler PF, Bonhoeffer LS, Tacker M, Schuster P. Fast folding and comparison of RNA secondary structures. Monatsh Chem. 1994;125:167-188.

    Not in our library

29. 29.

    Karolchik D, Kuhn RM, Baertsch R, Barber GP, Clawson H, Diekhans M, Giardine B, Harte RA, Hinrichs AS, Hsu F, Kober KM, Miller W, Pedersen JS, Pohl A, Raney BJ, Rhead B, Rosenbloom KR, Smith KE, Stanke M, Thakkapallayil A, Trumbower H, Wang T, Zweig AS, Haussler D, Kent WJ. The UCSCGenome Browser Database: 2008 update. Nucleic Acids Res. 2008;36:D773-D779.

    Not in our library10.1093/nar/gkm966

30. 30.

    Kinsella RJ, Kähäri A, Haider S, Zamora J, Proctor G, Spudich G, Almeida-King J, Staines D, Derwent P, Kerhornou A, Kersey P, Flicek P. Ensembl BioMarts: a hub for data retrieval across taxonomic space. Database. 2011;2011:bar030.

    Not in our library10.1093/database/bar030

31. 31.

    Kiryu H, Asai K. Rchange: algorithm for computing energy changes of RNA secondary structures in response to base mutations. Bioinformatics. 2012;28:1093-1101.

    Not in our library10.1093/bioinformatics/bts097

32. 32.

    Knudsen B, Hein J. Pfold: RNA secondary structure prediction using stochastic context-free grammars. Nucleic Acids Res. 2003;31:3423-3428.

    Not in our library10.1093/nar/gkg614

33. 33.

    Kruspe M, Stadler PF. Progressive multiple sequence alignments from triplets. BMC Bioinform. 2007;8:254.

    Not in our library10.1186/1471-2105-8-254

34. 34.

    Lam E, Kam A, Waldispühl J. corRna: a web server for predicting multiple-point deleterious mutations in structural RNAs. Nucleic Acids Res. 2011;39:W160-W166.

    Not in our library10.1093/nar/gkr358

35. 35.

    Lange SJ, Maticzka D, Möhl M, Gagnon JN, Brown CM, Backofen R. Global or local? Predicting secondary structure and accessibility in mRNAs. Nucleic Acids Res. 2012;40:5215-5226.

    Not in our library10.1093/nar/gks181

36. 36.

    Li MJ, Wang P, Liu X, Lim E, Wang Z, Yeager M, Wong MP, Sham PC, Chanock SJ, Wang J. GWASdb: a database for human genetic variants identified by genome-wide association studies. Nucleic Acids Res. 2012;40:D1047-D1054.

    Not in our library10.1093/nar/gkr1182

37. 37.
    ViennaRNA Package 2.0 · 2011

    No notice
38. 38.

    Manolio TA. Genome-wide association studies and assessment of the risk of disease. N Engl J Med. 2010;363:166-176.

    Not in our library10.1056/nejmra0905980

39. 39.

    Martin JS, Halvorsen M, Davis-Neulander L, Ritz J, Gopinath C, Beauregard A, Laederach A. Structural effects of linkage disequilibrium on the transcriptome. RNA. 2012;18:77-87.

    Not in our library10.1261/rna.029900.111

40. 40.

    Mathews DH, Disney MD, Childs JL, Schroeder SJ, Zuker M, Turner DH. Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure. Proc Natl Acad Sci USA. 2004;101:7287-7292.

    Not in our library10.1073/pnas.0401799101

Cited by papers we hold 3

• A pan-cancer analysis of synonymous mutations · 2019
  No notice
• OncodriveFML: a general framework to identify coding and non-coding regions with cancer driver mutations · 2016
  No notice
• The RNAsnp web server: predicting SNP effects on local RNA secondary structure · 2013
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.