Targeting of aberrant mRNAs to cytoplasmic processing bodies

Cell. 2006 Jun 16;125(6):1095-109. doi: 10.1016/j.cell.2006.04.037.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Codon, Nonsense
  • Cytoplasmic Structures / metabolism*
  • Models, Biological
  • RNA Helicases / genetics
  • RNA Helicases / metabolism
  • RNA Stability*
  • RNA Transport
  • RNA, Fungal / metabolism*
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Codon, Nonsense
  • NMD2 protein, S cerevisiae
  • RNA, Fungal
  • RNA, Messenger
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • UPF3 protein, S cerevisiae
  • NAM7 protein, S cerevisiae
  • RNA Helicases