RNAmotifs: Prediction of Multivalent RNA Motifs That Control Alternative Splicing

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2014 Feb 4

PMID 24485098

Citations 30

Authors

Matteo Cereda

Uberto Pozzoli

Gregor Rot

Peter Juvan

Anthony Schweitzer

Tyson Clark

Jernej Ule

Affiliations

Soon will be listed here.

Abstract

RNA-binding proteins (RBPs) regulate splicing according to position-dependent principles, which can be exploited for analysis of regulatory motifs. Here we present RNAmotifs, a method that evaluates the sequence around differentially regulated alternative exons to identify clusters of short and degenerate sequences, referred to as multivalent RNA motifs. We show that diverse RBPs share basic positional principles, but differ in their propensity to enhance or repress exon inclusion. We assess exons differentially spliced between brain and heart, identifying known and new regulatory motifs, and predict the expression pattern of RBPs that bind these motifs. RNAmotifs is available at https://bitbucket.org/rogrro/rna_motifs.

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References

Sickmier E, Frato K, Shen H, Paranawithana S, Green M, Kielkopf C . Structural basis for polypyrimidine tract recognition by the essential pre-mRNA splicing factor U2AF65. Mol Cell. 2006; 23(1):49-59. PMC: 2043114. DOI: 10.1016/j.molcel.2006.05.025. View

Polydorides A, Okano H, Yang Y, Stefani G, Darnell R . A brain-enriched polypyrimidine tract-binding protein antagonizes the ability of Nova to regulate neuron-specific alternative splicing. Proc Natl Acad Sci U S A. 2000; 97(12):6350-5. PMC: 18606. DOI: 10.1073/pnas.110128397. View

Auweter S, Oberstrass F, Allain F . Sequence-specific binding of single-stranded RNA: is there a code for recognition?. Nucleic Acids Res. 2006; 34(17):4943-59. PMC: 1635273. DOI: 10.1093/nar/gkl620. View

Singh R, Valcarcel J, Green M . Distinct binding specificities and functions of higher eukaryotic polypyrimidine tract-binding proteins. Science. 1995; 268(5214):1173-6. DOI: 10.1126/science.7761834. View

Witten J, Ule J . Understanding splicing regulation through RNA splicing maps. Trends Genet. 2011; 27(3):89-97. PMC: 3165201. DOI: 10.1016/j.tig.2010.12.001. View

Brudno M, Gelfand M, Spengler S, Zorn M, Dubchak I, Conboy J . Computational analysis of candidate intron regulatory elements for tissue-specific alternative pre-mRNA splicing. Nucleic Acids Res. 2001; 29(11):2338-48. PMC: 55704. DOI: 10.1093/nar/29.11.2338. View

Jensen K, Musunuru K, Lewis H, Burley S, Darnell R . The tetranucleotide UCAY directs the specific recognition of RNA by the Nova K-homology 3 domain. Proc Natl Acad Sci U S A. 2000; 97(11):5740-5. PMC: 18503. DOI: 10.1073/pnas.090553997. View

Llorian M, Schwartz S, Clark T, Hollander D, Tan L, Spellman R . Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB. Nat Struct Mol Biol. 2010; 17(9):1114-23. PMC: 2933513. DOI: 10.1038/nsmb.1881. View

Castle J, Zhang C, Shah J, Kulkarni A, Kalsotra A, Cooper T . Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines. Nat Genet. 2008; 40(12):1416-25. PMC: 3197713. DOI: 10.1038/ng.264. View

10.

Dember L, Kim N, Liu K, Anderson P . Individual RNA recognition motifs of TIA-1 and TIAR have different RNA binding specificities. J Biol Chem. 1996; 271(5):2783-8. DOI: 10.1074/jbc.271.5.2783. View

11.

Sugimoto Y, Konig J, Hussain S, Zupan B, Curk T, Frye M . Analysis of CLIP and iCLIP methods for nucleotide-resolution studies of protein-RNA interactions. Genome Biol. 2012; 13(8):R67. PMC: 4053741. DOI: 10.1186/gb-2012-13-8-r67. View

12.

Zhang C, Lee K, Swanson M, Darnell R . Prediction of clustered RNA-binding protein motif sites in the mammalian genome. Nucleic Acids Res. 2013; 41(14):6793-807. PMC: 3737533. DOI: 10.1093/nar/gkt421. View

13.

Hynes R . The extracellular matrix: not just pretty fibrils. Science. 2009; 326(5957):1216-9. PMC: 3536535. DOI: 10.1126/science.1176009. View

14.

Venables J, Klinck R, Koh C, Gervais-Bird J, Bramard A, Inkel L . Cancer-associated regulation of alternative splicing. Nat Struct Mol Biol. 2009; 16(6):670-6. DOI: 10.1038/nsmb.1608. View

15.

Zarnack K, Konig J, Tajnik M, Martincorena I, Eustermann S, Stevant I . Direct competition between hnRNP C and U2AF65 protects the transcriptome from the exonization of Alu elements. Cell. 2013; 152(3):453-66. PMC: 3629564. DOI: 10.1016/j.cell.2012.12.023. View

16.

Auweter S, Fasan R, Reymond L, Underwood J, Black D, Pitsch S . Molecular basis of RNA recognition by the human alternative splicing factor Fox-1. EMBO J. 2005; 25(1):163-73. PMC: 1356361. DOI: 10.1038/sj.emboj.7600918. View

17.

Zhang C, Zhang Z, Castle J, Sun S, Johnson J, Krainer A . Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2. Genes Dev. 2008; 22(18):2550-63. PMC: 2546699. DOI: 10.1101/gad.1703108. View

18.

Licatalosi D, Mele A, Fak J, Ule J, Kayikci M, Chi S . HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature. 2008; 456(7221):464-9. PMC: 2597294. DOI: 10.1038/nature07488. View

19.

Fujita P, Rhead B, Zweig A, Hinrichs A, Karolchik D, Cline M . The UCSC Genome Browser database: update 2011. Nucleic Acids Res. 2010; 39(Database issue):D876-82. PMC: 3242726. DOI: 10.1093/nar/gkq963. View

20.

Liu F, Walters K . Multitasking with ubiquitin through multivalent interactions. Trends Biochem Sci. 2010; 35(6):352-60. PMC: 3917509. DOI: 10.1016/j.tibs.2010.01.002. View