General translational repression by activators of mRNA decapping.
Translation and mRNA degradation are affected by a key transition where eukaryotic mRNAs exit translation and assemble an mRNP state that accumulates into processing bodies (P bodies), cytoplasmic sites of mRNA degradation containing non-translating mRNAs, and mRNA degradation machinery. We identify the decapping activators Dhh1p and Pat1p as functioning as translational repressors and facilitators of P body formation. Strains lacking both Dhh1p and Pat1p show strong defects in mRNA decapping and P body formation and are blocked in translational repression. Contrastingly, overexpression of Dhh1p or Pat1p causes translational repression, P body formation, and arrests cell growth. Dhh1p, and its human homolog, RCK/p54, repress translation in vitro, and Dhh1p function is bypassed in vivo by inhibition of translational initiation. These results identify a broadly acting mechanism of translational repression that targets mRNAs for decapping and functions in translational control. We propose this mechanism is competitively balanced with translation, and shifting this balance is an important basis of translational control.
Coller
Jeff
J
Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA.
Parker
Roy
R
D003594:Cytoplasmic Granules / Q000378:metabolism*; D053487:DEAD-box RNA Helicases; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D020868:Gene Silencing / Q000502:physiology*; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D020365:RNA Helicases / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D012316:RNA Nucleotidyltransferases / Q000235:genetics / Q000502:physiology; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D013997:Time Factors
D004268:DNA-Binding Proteins; C103266:PAT1 protein, S cerevisiae; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D012316:RNA Nucleotidyltransferases; C094683:DDX6 protein, human; C445083:DHH1 protein, S cerevisiae; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases