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Getting rid of faulty mRNA
The cell monitors the health of its mRNAs, destroying those that are faulty or damaged. Destruction by the exosome complex prevents them from being used to synthesize deranged and potentially dangerous proteins. Schmidt et al. determined the structure of the Ski helicase complex, which guides RNAs to the exosome complex destruction machinery in association with a mRNAbound ribosome. The end of the mRNA is threaded from the ribosome into the heart of the helicase, whence the message would be channeled into the maw of the exosome complex.
Science, this issue p. 1431
Abstract
Ski2-Ski3-Ski8 (Ski) is a helicase complex functioning with the RNA-degrading exosome to mediate the 3′-5′ messenger RNA (mRNA) decay in turnover and quality-control pathways. We report that the Ski complex directly associates with 80S ribosomes presenting a short mRNA 3′ overhang. We determined the structure of an endogenous ribosome-Ski complex using cryo–electron microscopy (EM) with a local resolution of the Ski complex ranging from 4 angstroms (Å) in the core to about 10 Å for intrinsically flexible regions. Ribosome binding displaces the autoinhibitory domain of the Ski2 helicase, positioning it in an open conformation near the ribosomal mRNA entry tunnel. We observe that the mRNA 3′ overhang is threaded directly from the small ribosomal subunit to the helicase channel of Ski2, primed for ongoing exosome-mediated 3′-5′ degradation.
