Argonaute2 Is Essential for Mammalian Gastrulation and Proper Mesoderm Formation 英文参考文献.docVIP

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Argonaute2 Is Essential for Mammalian Gastrulation and Proper Mesoderm Formation 英文参考文献.doc

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Argonaute2 Is Essential for Mammalian Gastrulation and Proper Mesoderm Formation 英文参考文献

Argonaute2IsEssentialforMammalian GastrulationandProperMesodermFormation Reid S.Alisch1,Peng Jin1,Michael Epstein1,Tamara Caspary1,Stephen T.Warren1,2,3* 1DepartmentofHumanGenetics,EmoryUniversitySchoolofMedicine,Atlanta,Georgia,UnitedStatesofAmerica,2DepartmentofBiochemistry,EmoryUniversitySchool ofMedicine,Atlanta,Georgia,UnitedStatesofAmerica,3DepartmentofPediatrics,EmoryUniversitySchoolofMedicine,Atlanta,Georgia,UnitedStatesofAmerica MammalianArgonauteproteins(EIF2C1à4)playanessentialroleinRNA-inducedsilencing.Here,weshowthattheloss of eIF2C2 (Argonaute2 or Ago2) results in gastrulation arrest, ectopic expression of Brachyury (T), and mesoderm expansion. We identify a genetic interaction between Ago2 and T, as Ago2 haploinsufficiency partially rescues the classic T/tshort-tail phenotype. Finally, we demonstrate that the ectopic T expression and concomitant mesoderm expansionresultfromdisruptedfibroblastgrowthfactorsignaling,likelyduetoaberrantexpressionofEomesodermin. Together,thesedataindicatethatafactorbestknownasakeycomponentoftheRNA-inducedsilencingcomplexis requiredforproperfibroblastgrowthfactorsignalingduringgastrulation,suggestingapossiblemicro-RNAfunctionin theformationofamammaliangermlayer. Citation:AlischRS,JinP,EpsteinM,CasparyT,WarrenST(2007)Argonaute2isessentialformammaliangastrulationandpropermesodermformation.PLoSGenet3(12): e227.doi:10.1371/journal.pgen.0030227 generate a mouse line that transmits an interrupted Ago2 allele without an obvious heterozygous phenotype. The Introduction Argonauteproteinscompriseahighlyconservedgenefamily necessary for a range of physiological and developmental processes.Theseproteinsarede?nedbythepresenceofPAZ and PIWI domains, which modulate proteinàprotein inter- actions, nucleic acid binding, and, in some cases, mRNA cleavage[1–5].Argonauteproteinsserveasscaffoldsfortarget- mRNA recognition by short regulatory guide RNAs during the process of RNA interference (RNAi) [6]. The Argonaute family was initially l