ABSTRACT
N onsense-mediated mRNA decay (NM D) is triggered by premature translation termination, but the features distinguishing that event from normal termination are unknown. One model for NM D in yeast suggests that decay-inducing factors bound to mRNA during early processing events are routinely removed by elongating ribosomes, but maintain an mRNA association when termination is premature, thereby triggering rapid turn over. Recent experiments challenge this notion and point to a model which posits that mRNA decay is activated by the intrinsically aberrant nature of premature termination. Toeprinting assays that delineate ribosome positioning demonstrate that premature translation termination in yeast extracts is indeed aberrant. Aberrant termination depends on prior nonsense codon recognition and is eliminated in extracts derived from cells lacking the principal NM D factors, Upflp or Nmd2p (Upf2p), or by flanking the nonsense codon with a normal 3'-untranslated region (UTR). Tethered poly (A)-binding protein (Pablp), used as a mimic of a normal 3-UTR, recruits the termination factor Sup35p (eRF3) and stabilizes nonsense-containing mRNAs. These findings indicate that efficient termination and mRNA stability are dependent on a properly configured З'-UTR and lead to a model specifying roles for Upflp, Nmd2p, and Upf3p that are exclusive to premature termination.
