Protein Modularity of Alternatively Spliced Exons Is Associated with Tissue-Specific Regulation of Alternative Splicing 英文参考文献.docVIP

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Protein Modularity of Alternatively Spliced Exons Is Associated with Tissue-Specific Regulation of Alternative Splicing 英文参考文献.doc

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Protein Modularity of Alternatively Spliced Exons Is Associated with Tissue-Specific Regulation of Alternative Splicing 英文参考文献

ProteinModularityofAlternativelySpliced ExonsIsAssociatedwithTissue-Specific RegulationofAlternativeSplicing YiXing, Christopher J.Lee* MolecularBiologyInstitute,andInstituteforGenomicsandProteomics,DepartmentofChemistryandBiochemistry,UniversityofCalifornia,LosAngeles,California,United StatesofAmerica Recent comparative genomic analysis of alternative splicing has shown that protein modularity is an important criterionforfunctionalalternativesplicingevents.Exonsthatarealternativelysplicedinmultipleorganismsaremuch morelikelytobeanexactmultipleof3ntinlength,representingaclassof‘‘modular’’exonsthatcanbeinsertedor removed from the transcripts without affecting the rest of the protein. To understand the precise roles of these modularexons,inthispaperwehaveanalyzedmicroarraydatafor3,126alternativelysplicedexonsacrosstenmouse tissues generated by Pan and coworkers. We show that modular exons are strongly associated with tissue-specific regulationofalternativesplicing.Exonsthatarealternativelysplicedatuniformlyhightranscriptinclusionlevelsor uniformlylowlevelsshownopreferenceforproteinmodularity.Incontrast,alternativelysplicedexonswithdramatic changesofinclusionlevelsacrossmousetissues(referredtoas‘‘tissue-switched’’exons)arebothstrikinglybiasedto be modular and are strongly conserved between human and mouse. The analysis of different subsets of tissue- switchedexonsshowsthattheincreasedproteinmodularitycannotbeexplainedbytheoverallexoninclusionlevel, butisspecificallyassociatedwithtissue-switchedalternativesplicing. Citation:XingY,LeeCJ(2005)Proteinmodularityofalternativelysplicedexonsisassociatedwithtissue-specificregulationofalternativesplicing.PLoSGenet1(3):e34. that are included in the majority of a gene’s transcripts. Instead, it is strikingly associated with ancestral alternative Introduction Recently,therehasbeengreatinterestincharacterizingthe functional selection pressures for alternative splicing by evolutionary genomics [1–4]. Ancestral alternative splicing