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SMG-6 mRNA cleavage stalls ribosomes near premature stop codons in vivo.

ABSTRACT: Nonsense-mediated mRNA decay (NMD) protects cells from the toxic and potentially dominant effects of truncated proteins. Targeting of mRNAs with early stop codons is mediated by the ribosome and spatiotemporally aligned with translation termination. Previously we identified a novel NMD intermediate: ribosomes stalled on cleaved stop codons, raising the possibility that NMD begins even prior to ribosome removal from the stop codon. Here we show that this intermediate is the result of mRNA cleavage by the endonuclease SMG-6. Our work supports a model in which ribosomes stall secondary to SMG-6 mRNA cleavage in Caenorhabditis elegans and humans, i.e. that the novel NMD intermediate occurs after a prior ribosome elicits NMD. Our genetic analysis of C. elegans' SMG-6 supports a central role for SMG-6 in metazoan NMD, and provides a context for evaluating its function in other metazoans.

SUBMITTER: Kim JH

PROVIDER: S-EPMC9410879 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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SMG-6 mRNA cleavage stalls ribosomes near premature stop codons in vivo.

Kim John H JH Modena Matthew S MS Sehgal Enisha E Courney Annie A Neudorf Celine W CW Arribere Joshua A JA

Nucleic acids research 20220801 15

Nonsense-mediated mRNA decay (NMD) protects cells from the toxic and potentially dominant effects of truncated proteins. Targeting of mRNAs with early stop codons is mediated by the ribosome and spatiotemporally aligned with translation termination. Previously we identified a novel NMD intermediate: ribosomes stalled on cleaved stop codons, raising the possibility that NMD begins even prior to ribosome removal from the stop codon. Here we show that this intermediate is the result of mRNA cleavag ...[more]

PMID: 35950494

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