Targeting of aberrant mRNAs to cytoplasmic processing bodies.

Department of Molecular and Cellular Biology, University of Arizona, Tucson, 85721, USA.
Cell (Impact Factor: 33.12). 07/2006; 125(6):1095-109. DOI: 10.1016/j.cell.2006.04.037
Source: PubMed

ABSTRACT 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.

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