Reprogramming of 3′ Untranslated Regions of mRNAs by Alternative Polyadenylation in Generation of Pluripotent Stem Cells from Different Cell Types 英文参考文献.docVIP

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Reprogramming of 3′ Untranslated Regions of mRNAs by Alternative Polyadenylation in Generation of Pluripotent Stem Cells from Different Cell Types 英文参考文献.doc

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Reprogramming of 3′ Untranslated Regions of mRNAs by Alternative Polyadenylation in Generation of Pluripotent Stem Cells from Different Cell Types 英文参考文献

Reprogrammingof39UntranslatedRegionsofmRNAsby AlternativePolyadenylationinGenerationofPluripotent StemCellsfromDifferentCellTypes ZheJi,BinTian* DepartmentofBiochemistryandMolecularBiology,GraduateSchoolofBiomedicalSciencesandNewJerseyMedicalSchool,UniversityofMedicineandDentistryofNew Jersey,Newark,NewJersey,UnitedStatesofAmerica Abstract Background: The 39 untranslated regions (39UTRs) of mRNAs contain cis elements involved in post-transcriptional regulation of gene expression. Over half of all mammalian genes contain multiple polyadenylation sites that lead to different39UTRsforagene.Studieshaveshownthatthealternativepolyadenylation(APA)patternvariesacrosstissues,and isdynamicallyregulatedinproliferatingordifferentiatingcells.Generationofinducedpluripotentstem(iPS)cells,inwhich differentiatedcellsarereprogrammedtoanembryonicstem(ES)cell-likestate,hasbeenintensivelystudiedinrecentyears. However,itisnotknownhow39UTRsareregulatedduringcellreprogramming. Methods/MainFindings:UsingacomputationalmethodthatrobustlyexaminesAPAacrossDNAmicroarraydatasets,we analyzed 39UTR dynamics in generation of iPS cells from different cell types. We found that 39UTRs shorten during reprogrammingofsomaticcells,theextentofwhichdependsonthetypeofsourcecell.Bycontrast,reprogrammingof spermatogonialcellsinvolves39UTRlengthening.Thealternativepolyadenylationsitesthatarehighlyresponsivetochange of cell state in generation of iPS cells are also highly regulated during embryonic development in opposite directions. Comparedwithothersites,theyaremoreconserved,canleadtolongeralternative39UTRs,andareassociatedwithmorecis elementsforpolyadenylation.Consistently,reprogrammingofsomaticcellsandgermcellsinvolvessignificantupregulation and downregulation, respectively, of mRNAs encoding polyadenylation factors, and RNA processing is one of the most significantly regulated biological processes during cell reprogramming. Furthermore, genes containing target sites of ES cell-specific microRNAs (miRNAs) i