Nonsense-mediated decay triggers nonstop mRNA decay in a metazoan

Eukaryotic mRNAs lacking stop codons are degraded in a process called nonstop mRNA decay. Much of our knowledge of nonstop mRNA decay comes from seminal work in S. cerevisiae. Here we develop an experimental system (C. elegans) to study nonstop mRNA decay in metazoa. We present data in support of a nonstop decay mechanism conserved from S. cerevisiae to C. elegans. In contrast to S. cerevisiae however, C. elegans exhibits a higher degree of endogenous mRNAs that are nonstop decay targets, including ~700 mRNAs. Surprisingly, this group has a high overlap with endogenous nonsense-mediated mRNA decay targets. Nonsense decay removes the products of early translation termination, and is thought of as a fundamentally different process from nonstop in both mechanism and machinery. We present data in support of a model wherein nonsense-mediated decay funnels into the nonstop decay pathway in C. elegans. Our results point to SKI-exosome decay and pelota-based ribosome removal as additional steps in nonsense-mediated decay. In summary: we (1) present tools and a new model system (C. elegans) for the study of nonstop mRNA decay, (2) demonstrate the mechanism of and machinery for nonstop decay is conserved from yeast to C. elegans, and (3) identify an unexpected link between nonsense and nonstop decay.