Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay.
Decapping is a key step in general and regulated mRNA decay. In Saccharomyces cerevisiae it constitutes a rate-limiting step in the nonsense-mediated decay pathway that rids cells of mRNAs containing premature termination codons. Here two human decapping enzymes are identified, hDcp1a and hDcp2, as well as a homolog of hDcp1a, termed hDcp1b. Transiently expressed hDcp1a and hDcp2 proteins localize primarily to the cytoplasm and form a complex in human cell extracts. hDcp1a and hDcp2 copurify with decapping activity, an activity sensitive to mutation of critical hDcp residues. Importantly, coimmunoprecipitation assays demonstrate that hDcp1a and hDcp2 interact with the nonsense-mediated decay factor hUpf1, both in the presence and in the absence of the other hUpf proteins, hUpf2, hUpf3a, and hUpf3b. These data suggest that a human decapping complex may be recruited to mRNAs containing premature termination codons by the hUpf proteins.
Lykke-Andersen
Jens
J
Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA. Jens.Lykke-Andersen@colorado.edu
D002460:Cell Line; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D009154:Mutation; D014176:Protein Biosynthesis; D039381:RNA Cap-Binding Proteins; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D012331:RNA, Fungal; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D005656:Fungal Proteins; D009097:Multienzyme Complexes; D039381:RNA Cap-Binding Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; C100868:DCP1 protein, S cerevisiae; C400572:DCP2 protein, S cerevisiae; D004722:Endoribonucleases; C466279:DCP1A protein, human; C467723:DCP2 protein, human; C074151:NAM7 protein, S cerevisiae; D020365:RNA Helicases; C101828:UPF1 protein, human