Overlapping Functions of Argonaute Proteins in Patterning and Morphogenesis of Drosophila Embryos 英文参考文献.docVIP

OverlappingFunctionsofArgonaute ProteinsinPatterningandMorphogenesis ofDrosophilaEmbryos Wibke J.Meyer1,Silke Schreiber1,YiGuo2¤a,Thorsten Volkmann1,Michael A.Welte2*,H.Arno J.Mu¨ller1¤b* 1Institutfu¨rGenetik,Heinrich-HeineUniversita¨t, Du¨sseldorf,Germany,2DepartmentofBiology,BrandeisUniversity,Waltham,Massachusetts,UnitedStatesofAmerica Argonaute proteins are essential components of the molecular machinery that drives RNA silencing. In Drosophila, differentmembersoftheArgonautefamilyofproteinshavebeenassignedtodistinctRNAsilencingpathways.While Ago1isrequiredformicroRNAfunction,Ago2isacrucialcomponentoftheRNA-inducedsilencingcomplexinsiRNA- triggered RNA interference. Drosophila Ago2 contains an unusual amino-terminus with two types of imperfect glutamine-richrepeats(GRRs)ofunknownfunction.HereweshowthattheGRRsofAgo2areessentialforthenormal function of the protein. Alleles with reduced numbers of GRRs cause specific disruptions in two morphogenetic processesassociatedwiththemidblastulatransition:membranegrowthandmicrotubule-basedorganelletransport. These defects do not appear to result from disruption of siRNA-dependent processes but rather suggest an interference of the mutant Ago2 proteins in an Ago1-dependent pathway. Using loss-of-function alleles, we further demonstratethatAgo1andAgo2actinapartiallyredundantmannertocontroltheexpressionofthesegment-polarity gene wingless in the early embryo. Our findings argue against a strict separation of Ago1 and Ago2 functions and suggest that these proteins act in concert to control key steps of the midblastula transition and of segmental patterning. Citation:MeyerWJ,SchreiberS,GuoY,VolkmannT,WelteMA,etal.(2006)OverlappingfunctionsofArgonauteproteinsinpatterningandmorphogenesisofDrosophila embryos.PLoSGenet2(8):e134.DOI:10.1371/journal.pgen.0020134 in that it has a unique amino-terminal extension rich in glutamines (37% of all residues are glutamine). Almost two- Introduction RNA silencing represents an importan