Targeting of aberrant mRNAs to cytoplasmic processing bodies.
In eukaryotes, a specialized pathway of mRNA degradation termed nonsense-mediated decay (NMD) functions in mRNA quality control by recognizing and degrading mRNAs with aberrant termination codons. We demonstrate that NMD in yeast targets premature termination codon (PTC)-containing mRNA to P-bodies. Upf1p is sufficient for targeting mRNAs to P-bodies, whereas Upf2p and Upf3p act, at least in part, downstream of P-body targeting to trigger decapping. The ATPase activity of Upf1p is required for NMD after the targeting of mRNAs to P-bodies. Moreover, Upf1p can target normal mRNAs to P-bodies but not promote their degradation. These observations lead us to propose a new model for NMD wherein two successive steps are used to distinguish normal and aberrant mRNAs.
Sheth
Ujwal
U
Department of Molecular and Cellular Biology, University of Arizona, Tucson, 85721, USA.
Parker
Roy
R
D048868:Adaptor Proteins, Signal Transducing; D018389:Codon, Nonsense; D022083:Cytoplasmic Structures / Q000378:metabolism*; D008954:Models, Biological; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability; D034443:RNA Transport; D012331:RNA, Fungal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018389:Codon, Nonsense; C092470:NMD2 protein, S cerevisiae; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; C096360:UPF3 protein, S cerevisiae; C074151:NAM7 protein, S cerevisiae; D020365:RNA Helicases