A New Splice Variant of the Mouse SIRT3 Gene Encodes the Mitochondrial Precursor Protein 英文参考文献.docVIP

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A New Splice Variant of the Mouse SIRT3 Gene Encodes the Mitochondrial Precursor Protein 英文参考文献.doc

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A New Splice Variant of the Mouse SIRT3 Gene Encodes the Mitochondrial Precursor Protein 英文参考文献

ANewSpliceVariantoftheMouseSIRT3GeneEncodes theMitochondrialPrecursorProtein HelenM.Cooper1.,Jing-YiHuang2.,EricVerdin2,JohannesN.Spelbrink1* 1University of Tampere, Institute of Medical Technology and Tampere University Hospital, Tampere, Finland, 2Gladstone Institute of Virology and Immunology, UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica Abstract Background:MammalshavesevenNAD-dependentproteindeacetylases.Theseproteins,calledsirtuins,arehomologousto yeastSir2,andareemergingasimportantregulatorsoflifespanandintermediarymetabolism.Threemammaliansirtuins, SIRT3-5aremitochondrial.Sirtuinsarehighlyconservedbetweenspecies,yetmouseSIRT3wasreportedtobemarkedly shorterthanitshumancounterpartandtolacktheN-terminalmitochondrialtargetingsignalpresentinthehumanprotein. Results:WehaveisolatedanovelmouseSIRT3splicevariant.ThiscDNAcontainstwotranslationinitiationcodonsupstream oftheoriginallyreportedstartsite.Weshow,usingimmunofluorescenceandproteinexpressionanalysisthattheselonger variantsareexpressedandefficientlytargetedtomitochondria,andthattheprocessedformsoftheselongervariantsare identical in size to the endogenous mouse SIRT3. We also show that the previously described form of SIRT3 is not mitochondrial. Conclusions:OurobservationspointtoahighlevelofconservationofSIRT3asamitochondrialproteininmiceandhuman andindicatethatseveralpreviousstudies,whichaddressedmouseSirt3function,needtobere-evaluated. Citation:CooperHM,HuangJ-Y,VerdinE,SpelbrinkJN(2009)ANewSpliceVariantoftheMouseSIRT3GeneEncodestheMitochondrialPrecursorProtein.PLoS ONE4(3):e4986.doi:10.1371/journal.pone.0004986 Editor:GrzegorzKudla,UniversityofEdinburgh,UnitedKingdom ReceivedDecember1,2008;AcceptedFebruary14,2009;PublishedMarch31,2009 Copyright: ? 2009 Cooper et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcear