Noisy Splicing Drives mRNA Isoform Diversity in Human Cells 英文参考文献.docVIP

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Noisy Splicing Drives mRNA Isoform Diversity in Human Cells 英文参考文献.doc

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Noisy Splicing Drives mRNA Isoform Diversity in Human Cells 英文参考文献

NoisySplicingDrivesmRNAIsoformDiversityinHuman Cells JosephK.Pickrell1*,AthmaA.Pai1*,YoavGilad1*,JonathanK.Pritchard1,2* 1DepartmentofHumanGenetics,TheUniversityofChicago,Chicago,Illinois,UnitedStatesofAmerica,2HowardHughesMedicalInstitute,TheUniversityofChicago, Chicago,Illinois,UnitedStatesofAmerica Abstract Whilethemajorityofmultiexonichumangenesshowsomeevidenceofalternativesplicing,itisunclearwhatfractionof observedspliceformsisfunctionallyrelevant.Inthisstudy,weexaminetheextentofalternativesplicinginhumancells usingdeepRNAsequencinganddenovoidentificationofsplicejunctions.Wedemonstratetheexistenceofalargeclassof lowabundanceisoforms,encompassingapproximately150,000previouslyunannotatedsplicejunctionsinourdata.Newly- identifiedsplicesitesshowlittleevidenceofevolutionaryconservation,suggestingthatthemajorityareduetoerroneous splice site choice. We show that sequence motifs involved in the recognition of exons are enriched in the vicinity of unconservedsplicesites.Weestimatethattheaverageintronhasasplicingerrorrateofapproximately0.7%andshowthat introns in highly expressed genes are spliced more accurately, likely due to their shorter length. These results implicate noisysplicingasanimportantpropertyofgenomeevolution. Citation:PickrellJK,PaiAA,GiladY,PritchardJK(2010)NoisySplicingDrivesmRNAIsoformDiversityinHumanCells.PLoSGenet6(12):e1001236.doi:10.1371/ journal.pgen.1001236 Editor:EmmanouilT.Dermitzakis,UniversityofGenevaMedicalSchool,Switzerland ReceivedJuly4,2010;AcceptedNovember3,2010;PublishedDecember9,2010 Copyright: ? 2010 Pickrell et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbytheHHMIandbyNIHgrantsMH084703-01toJKPritchardandGM077959toYGilad.Thefundershadnoroleinstudy design,datacollectionandanalysis,decisiontopublish,orpreparationofthemanuscript. C