RNAcontext A New Method for Learning the Sequence and Structure Binding Preferences of RNA-Binding Proteins 英文参考文献.docVIP

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RNAcontext A New Method for Learning the Sequence and Structure Binding Preferences of RNA-Binding Proteins 英文参考文献.doc

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RNAcontext A New Method for Learning the Sequence and Structure Binding Preferences of RNA-Binding Proteins 英文参考文献

RNAcontext:ANewMethodforLearningtheSequence andStructureBindingPreferencesofRNA-Binding Proteins HilalKazan1,DebashishRay2,EstherT.Chan3,TimothyR.Hughes2,3,4,QuaidMorris1,2,3,4 * 1DepartmentofComputerScience,UniversityofToronto,Toronto,Ontario,Canada,2BantingandBestDepartmentofMedicalResearch,UniversityofToronto,Toronto, Ontario, Canada, 3Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada, 4Donnelley Centre for Cellular and Biomolecular Research, UniversityofToronto,Toronto,Ontario,Canada Abstract Metazoan genomes encode hundreds of RNA-binding proteins (RBPs). These proteins regulate post-transcriptional gene expressionandhavecriticalrolesinnumerouscellularprocessesincludingmRNAsplicing,export,stabilityandtranslation. Despitetheirubiquityandimportance,thebindingpreferencesformostRBPsarenotwellcharacterized.Invitroandinvivo studies,usingaffinityselection-basedapproaches,havesuccessfullyidentifiedRNAsequenceassociatedwithspecificRBPs; however,itisdifficulttoinferRBPsequenceandstructuralpreferenceswithoutspecificallydesignedmotiffindingmethods. In this study, we introduce a new motif-finding method, RNAcontext, designed to elucidate RBP-specific sequence and structuralpreferenceswithgreateraccuracythanexistingapproaches.WeevaluatedRNAcontextonrecentlypublishedin vitro and in vivo RNA affinity selected data and demonstrate that RNAcontext identifies known binding preferences for several control proteins including HuR, PTB, and Vts1p and predicts new RNA structure preferences for SF2/ASF, RBM4, FUSIP1 and SLM2. The predicted preferences for SF2/ASF are consistent with its recently reported in vivo binding sites. RNAcontext is an accurate and efficient motif finding method ideally suited for using large-scale RNA-binding affinity datasetstodeterminetherelativebindingpreferencesofRBPsforawiderangeofRNAsequencesandstructures. Citation:KazanH,RayD,ChanET,HughesTR,MorrisQ(2010)RNAcontext:ANewMethodforLearningtheSequenceandStructureBindingPref