Exclusion of Exon 2 Is a Common mRNA Splice Variant of Primate Telomerase Reverse Transcriptases 英文参考文献.docVIP

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Exclusion of Exon 2 Is a Common mRNA Splice Variant of Primate Telomerase Reverse Transcriptases 英文参考文献.doc

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Exclusion of Exon 2 Is a Common mRNA Splice Variant of Primate Telomerase Reverse Transcriptases 英文参考文献

ExclusionofExon2IsaCommonmRNASpliceVariantof PrimateTelomeraseReverseTranscriptases JohannaB.Withers¤,TamaraAshvetiya,KarenL.Beemon* DepartmentofBiology,TheJohnsHopkinsUniversity,Baltimore,Maryland,UnitedStatesofAmerica Abstract Telomericsequencesareaddedbyanenzymecalledtelomerasethatismadeoftwocomponents:acatalyticproteincalled telomerase reverse transcriptase (TERT) and an integral RNA template (TR). Telomerase expression is tightly regulatedat eachstepofgeneexpression,includingalternativesplicingofTERTmRNA.Whileoveradozendifferentalternativesplicing eventshavebeenreportedforhumanTERTmRNA,thesewereallinthe39halfofthecodingregion.Wewereinterestedin examiningsplicingofthe59halfofhTERTmRNA,especiallysinceexon2isunusuallylarge(1.3kb).Internalmammalian exonsareusuallyshort,typicallyonly50to300nucleotides,andmostlonginternalexonsarealternativelyprocessed.We used quantitative RT-PCR and high-throughput sequencing data to examine the variety and quantity of mRNA species generatedfromthehTERTlocus.Wedeterminedthatthereareapproximately20–40moleculesofhTERTmRNApercellin theA431humancellline.Inaddition,wedescribeanabundant,alternatively-splicedmRNAvariantthatexcludesTERTexon 2 and was seen in other primates. This variant causes a frameshift and results in translation termination in exon 3, generatinga12kDapolypeptide. Citation:WithersJB,AshvetiyaT,BeemonKL(2012)ExclusionofExon2IsaCommonmRNASpliceVariantofPrimateTelomeraseReverseTranscriptases.PLoS ONE7(10):e48016.doi:10.1371/journal.pone.0048016 Editor:BinTian,UMDNJ-NewJerseyMedicalSchool,UnitedStatesofAmerica ReceivedJuly6,2012;AcceptedSeptember25,2012;PublishedOctober24,2012 Copyright: ? 2012 Withers 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:FundingprovidedbyPublicHealthServiceGrantsRO1CA124596andRO1CA48746fromtheNationalCancerInst