Pre-mRNA splicing and human disease - Genes & Development

The precision and complexity of intron removal during pre-mRNA splicing still ... contain introns and that most pre-mRNAs undergo alternative splicing, ... Skiptomainpagecontent HOME ABOUT SUBMIT SUBSCRIBE ADVERTISE AUTHORINFO ARCHIVE CONTACT HELP SearchforKeyword: GO AdvancedSearch Pre-mRNAsplicingandhumandisease NunoAndréFaustino1,3and ThomasA.Cooper1,2,4 Departmentsof1Pathologyand 2MolecularandCellularBiology,BaylorCollegeofMedicine,Houston,Texas77030,USA; 3GraduatePrograminBasicandAppliedBiology,ICBAS,UniversityofOporto,Portugal Thisextractwascreatedintheabsenceofanabstract. Theprecisionandcomplexityofintronremovalduringpre-mRNAsplicingstillamazeseven26yearsafterthediscoverythat thecodinginformationofmetazoangenesisinterruptedbyintrons(Bergetetal.1977;Chowetal.1977).AddingtothisamazementistherecentrealizationthatmosthumangenesexpressmorethanonemRNAbyalternativesplicing, aprocessbywhichfunctionallydiverseproteinisoformscanbeexpressedaccordingtodifferentregulatoryprograms.Given thatthevastmajorityofhumangenescontainintronsandthatmostpre-mRNAsundergoalternativesplicing,itisnotsurprising thatdisruptionofnormalsplicingpatternscancauseormodifyhumandisease.Thepurposeofthisreviewistohighlight thedifferentmechanismsbywhichdisruptionofpre-mRNAsplicingplayaroleinhumandisease.Severalexcellentreviews providedetailedinformationonsplicingandtheregulationofsplicing(Burgeetal.1999;HastingsandKrainer2001;Black2003).Thepotentialroleofsplicingasamodifierofhumandiseasehasalsorecentlybeenreviewed(Nissim-RafiniaandKerem2002). Constitutivesplicingandthebasalsplicing machinery Thetypicalhumangenecontainsanaverageof8exons.Internalexonsaverage145nucleotides(nt)inlength,andintrons averagemorethan10timesthissizeandcanbemuchlarger(Landeretal.2001).Exonsaredefinedbyrathershortanddegenerateclassicalsplice-sitesequencesattheintron/exonborders(5′splice site,3′splicesite,andbranchsite;Fig.1A).Componentsofthebasalsplicingmachinerybindtotheclassicalsplice-site sequencesandpromoteassemblyofthemulticomponentsplicingcomplexknownasthespliceosome.Thespliceosomeperformsthe twoprimaryfunctionsofsplicing:recognitionoftheintron/exonboundariesandcatalysisofthecut-and-pastereactions thatremoveintronsandjoinexons.Thespliceosomeismadeupoffivesmallnuclearribonucleoproteins(snRNPs)… [FullTextofthisArticle] CiteULike Delicious Digg Facebook Reddit Twitter What'sthis? «Previous|NextArticle» TableofContents ThisArticle doi: 10.1101/gad.1048803 Genes&Dev. 2003. 17: 419-437 ColdSpringHarborLaboratoryPress »ExtractFree FullTextFree FullText(PDF)Free ArticleCategory REVIEW Services Alertmewhenthisarticleiscited Alertmeifacorrectionisposted Similararticlesinthisjournal SimilararticlesinWebofScience SimilararticlesinPubMed Downloadtocitationmanager Permissions CitingArticles Loadcitingarticleinformation CitingarticlesviaWebofScience CitingarticlesviaGoogleScholar GoogleScholar ArticlesbyFaustino,N.A. ArticlesbyCooper,T.A. Searchforrelatedcontent PubMed/NCBI PubMedcitation ArticlesbyFaustino,N.A. ArticlesbyCooper,T.A. RelatedContent Post-transcriptionalControl CancerandDiseaseModels Share CiteULike Delicious Digg Facebook Reddit Twitter What'sthis? G&DMostRead Viewall... Tweetsby@genesdev CurrentIssue May1,2022,36(9-10) InThisIssue ExportingNORADandotherintronlessGC-richRNAstothecytoplasm Regulatingsenescencesurveillance NovelroleofmiRNAclusterinsuppressinglungcancergrowthandmetastasis AlertmetonewissuesofG&D AdvanceOnlineArticles SubmitaManuscript G&DintheNews EditorialBoard AuthorInformation E-mailAlerts&RSSFeeds RecommendtoYourLibrary JobOpportunities   Home About Submit Subscribe Advertise AuthorInfo Archive Contact Help Copyright©2022byColdSpringHarborLaboratoryPress PrintISSN: 0890-9369 OnlineISSN: 1549-5477