Differential Impact of the HEN1 Homolog HENN-1 on 21U and 26G RNAs in the Germline of Caenorhabditis elegans 英文参考文献.docVIP
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Differential Impact of the HEN1 Homolog HENN-1 on 21U and 26G RNAs in the Germline of Caenorhabditis elegans 英文参考文献
DifferentialImpactoftheHEN1HomologHENN-1on21U
and26GRNAsintheGermlineofCaenorhabditiselegans
LeonieM.Kamminga1.¤a,JosienC.vanWolfswinkel1.¤b,MaartjeJ.Luteijn1.,LucasJ.T.Kaaij1,
MarloesP.Bagijn2,AlexandraSapetschnig2,EricA.Miska2,EugeneBerezikov1,Rene′ F.Ketting1*
1Hubrecht Institute–KNAW and University Medical Centre Utrecht, Utrecht, The Netherlands, 2Wellcome Trust/Cancer Research UK Gurdon Institute, University of
Cambridge,Cambridge,UnitedKingdom
Abstract
RNAinterference(RNAi)–relatedpathwaysaffectgeneactivitybysequence-specificrecruitmentofAgoproteinstomRNA
target molecules. The sequence specificity of this process stems from small RNA (sRNA) co-factors bound by the Ago
protein.StabilityofsRNAmoleculesinsomepathwaysisinpartregulatedbyHen1-mediatedmethylationoftheir39ends.
Here we describe the effects of the Caenorhabditis elegans HEN1 RNA–methyl-transferase homolog, HENN-1, on the
differentRNAipathwaysinthisnematode.WerevealdifferentialeffectsofHENN-1onthetwopathwaysthatareknownto
employmethylatedsRNAmolecules:the26Gand21Upathways.Surprisingly,inthegermline,stabilityof21URNAs,theC.
eleganspiRNAs,isonlymildlyaffectedbylossofmethylation;andintroductionofartificial21UtargetRNAdoesnotfurther
destabilizenon-methylated21URNAs.Incontrast,most26GRNAsdisplayreducedstabilityandrespondtolossofHENN-1
bydisplayingincreased39-uridylationfrequencies.Withinthe26GRNAclass,wefindthatspecificallyERGO-1–bound26G
RNAs are modified by HENN-1, while ALG-3/ALG-4–bound 26G RNAs are not. Global gene expression analysis of henn-1
mutantsrevealsmildeffects,includingdown-regulationofmanygermline-expressedgenes.Ourdatasuggestthat,apart
fromdirecteffectsofreduced26GRNAlevelsofhenn-1ongeneexpression,mosteffectsonglobalgeneexpressionare
indirect. These studies further refine our understanding of endogenous RNAi in C. elegans and the roles for Hen1 like
enzymesinthesepathways.
Citation:KammingaLM,vanWolfswinkelJC,LuteijnMJ,KaaijLJT,BagijnMP,etal.(2012)DifferentialImpactoftheHEN1HomologH
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