C. elegans Nucleostemin Is Required for Larval Growth and Germline Stem Cell Division 英文参考文献.docVIP

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C. elegans Nucleostemin Is Required for Larval Growth and Germline Stem Cell Division 英文参考文献.doc

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C.elegansNucleosteminIsRequiredforLarvalGrowth andGermlineStemCellDivision MichelleM.Kudron,ValerieReinke* DepartmentofGenetics,YaleUniversitySchoolofMedicine,NewHaven,Connecticut,UnitedStatesofAmerica Abstract Thenucleolushasshowntobeintegralformanyprocessesrelatedtocellgrowthandproliferation.Stemcellsinparticular arelikelytodependuponnucleolus-basedprocessestoremaininaproliferativestate.Ahighlyconservednucleolarfactor namednucleosteminisproposedtobeacriticallinkbetweennucleolarfunctionandstem-cell–specificprocesses.Currently, itisunclearwhethernucleosteminmodulatesproliferationbyaffectingribosomebiogenesisorbyanothernucleolus-based activity that is specific to stem cells and/or highly proliferating cells. Here, we investigate nucleostemin (nst-1) in the nematodeC.elegans,whichenablesustoexaminenst-1functionduringbothproliferationanddifferentiationinvivo.Like mammaliannucleostemin,theNST-1proteinislocalizedtothenucleolusandthenucleoplasm;however,itsexpressionis found in both differentiated and proliferating cells. Global loss of C. elegans nucleostemin (nst-1) leads to a larval arrest phenotypeduetoagrowthdefectinthesoma,whilelossofnst-1specificallyinthegermlinecausesgermlinestemcellsto undergo a cell cycle arrest. nst-1 mutants exhibit reduced levels of rRNAs, suggesting defects in ribosome biogenesis. However,NST-1isgenerallynotpresentinregionsofthenucleoluswhererRNAtranscriptionandprocessingoccurs,sothis reductionislikelysecondarytoadifferentdefectinribosomebiogenesis.TransgenicstudiesindicatethatNST-1requiresits N-terminaldomainforstableexpressionandbothitsG1GTPaseandintermediatedomainsforpropergermlinefunction. OurdatasupportaroleforC.elegansnucleosteminincellgrowthandproliferationbypromotingribosomebiogenesis. Citation: Kudron MM, Reinke V (2008) C. elegans Nucleostemin Is Required for Larval Growth and Germline Stem Cell Division. PLoS Genet 4(8): e1000181. doi:10.1371/journal.pgen.1000181 Editor:StuartK.Kim,StanfordUniversityMedicalCenter,UnitedStatesofAm