During canonical translation, ribosomes terminate when they encounter a stop codon in the mRNA (Figure 1A). In eukaryotes, the stop codon is recognized by the eukaryotic release factor eRF1, which is delivered in complex with eRF3 (Dever and Green, 2012). Hydrolysis of GTP to GDP by eRF3 leads to dissociation of eRF3 from the ribosome, allowing binding of the ATP-binding cassette protein ABCE1. ABCE1 works in concert with eRF1 to catalyze release of the completed polypeptide chain and to dissociate and recycle the posttermination complex components for the next round of translation (Dever and Green, 2012). However, ribosomes that translate damaged or truncated mRNAs that lack a stop codon cannot enter into the canonical translation termination pathway and therefore become stalled at the 30 end of the mRNA (Franckenberg et al., 2012). Studies using synthetic reporters have demonstrated that Dom34 rescues ribosomes stalled on these damaged mRNAs (Shao et al., 2013; Tsuboi et al., 2012); however, bone fide Dom34 mRNA substrates in vivo have not yet been identified. In a new study in this issue of Cell, Guydosh and Green (2014) employ ribosome profiling (Ingolia et al., 2009) to globally monitor the position, occupancy, and distribution of ribosomes on mRNAs in wild-type yeast (S. cerevisiae) as well as a yeast strain lacking Dom34 (dom34D). As expected, Dom34 is indeed observed to recycle ribosomes stalled at the 30 end of truncated mRNAs, such as the HAC1 mRNA. Unexpectedly, Dom34 also recycles ribosomes from the noncoding region of many cellular mRNAs.
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