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SMG-6 mRNA cleavage stalls ribosomes near premature stop codons in vivo
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:...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9410879/ https://www.ncbi.nlm.nih.gov/pubmed/35950494 http://dx.doi.org/10.1093/nar/gkac681 |
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author | Kim, John H Modena, Matthew S Sehgal, Enisha Courney, Annie Neudorf, Celine W Arribere, Joshua A |
author_facet | Kim, John H Modena, Matthew S Sehgal, Enisha Courney, Annie Neudorf, Celine W Arribere, Joshua A |
author_sort | Kim, John H |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9410879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-94108792022-08-26 SMG-6 mRNA cleavage stalls ribosomes near premature stop codons in vivo Kim, John H Modena, Matthew S Sehgal, Enisha Courney, Annie Neudorf, Celine W Arribere, Joshua A Nucleic Acids Res RNA and RNA-protein complexes 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. Oxford University Press 2022-08-11 /pmc/articles/PMC9410879/ /pubmed/35950494 http://dx.doi.org/10.1093/nar/gkac681 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | RNA and RNA-protein complexes Kim, John H Modena, Matthew S Sehgal, Enisha Courney, Annie Neudorf, Celine W Arribere, Joshua A SMG-6 mRNA cleavage stalls ribosomes near premature stop codons in vivo |
title | SMG-6 mRNA cleavage stalls ribosomes near premature stop codons in vivo |
title_full | SMG-6 mRNA cleavage stalls ribosomes near premature stop codons in vivo |
title_fullStr | SMG-6 mRNA cleavage stalls ribosomes near premature stop codons in vivo |
title_full_unstemmed | SMG-6 mRNA cleavage stalls ribosomes near premature stop codons in vivo |
title_short | SMG-6 mRNA cleavage stalls ribosomes near premature stop codons in vivo |
title_sort | smg-6 mrna cleavage stalls ribosomes near premature stop codons in vivo |
topic | RNA and RNA-protein complexes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9410879/ https://www.ncbi.nlm.nih.gov/pubmed/35950494 http://dx.doi.org/10.1093/nar/gkac681 |
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