Structure of the Nmd4-Upf1 complex supports conservation of the nonsense-mediated mRNA decay pathway between yeast and humans.
The nonsense-mediated mRNA decay (NMD) pathway clears eukaryotic cells of mRNAs containing premature termination codons (PTCs) or normal stop codons located in specific contexts. It therefore plays an important role in gene expression regulation. The precise molecular mechanism of the NMD pathway ha...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-09-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3002821 |
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| author | Irène Barbarin-Bocahu Nathalie Ulryck Amandine Rigobert Nadia Ruiz Gutierrez Laurence Decourty Mouna Raji Bhumika Garkhal Hervé Le Hir Cosmin Saveanu Marc Graille |
| author_facet | Irène Barbarin-Bocahu Nathalie Ulryck Amandine Rigobert Nadia Ruiz Gutierrez Laurence Decourty Mouna Raji Bhumika Garkhal Hervé Le Hir Cosmin Saveanu Marc Graille |
| author_sort | Irène Barbarin-Bocahu |
| collection | DOAJ |
| description | The nonsense-mediated mRNA decay (NMD) pathway clears eukaryotic cells of mRNAs containing premature termination codons (PTCs) or normal stop codons located in specific contexts. It therefore plays an important role in gene expression regulation. The precise molecular mechanism of the NMD pathway has long been considered to differ substantially from yeast to metazoa, despite the involvement of universally conserved factors such as the central ATP-dependent RNA-helicase Upf1. Here, we describe the crystal structure of the yeast Upf1 bound to its recently identified but yet uncharacterized partner Nmd4, show that Nmd4 stimulates Upf1 ATPase activity and that this interaction contributes to the elimination of NMD substrates. We also demonstrate that a region of Nmd4 critical for the interaction with Upf1 in yeast is conserved in the metazoan SMG6 protein, another major NMD factor. We show that this conserved region is involved in the interaction of SMG6 with UPF1 and that mutations in this region affect the levels of endogenous human NMD substrates. Our results support the universal conservation of the NMD mechanism in eukaryotes. |
| format | Article |
| id | doaj-art-88b8a87f5bd744cabe9e8d17925f9b6d |
| institution | DOAJ |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-88b8a87f5bd744cabe9e8d17925f9b6d2025-08-20T02:59:46ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852024-09-01229e300282110.1371/journal.pbio.3002821Structure of the Nmd4-Upf1 complex supports conservation of the nonsense-mediated mRNA decay pathway between yeast and humans.Irène Barbarin-BocahuNathalie UlryckAmandine RigobertNadia Ruiz GutierrezLaurence DecourtyMouna RajiBhumika GarkhalHervé Le HirCosmin SaveanuMarc GrailleThe nonsense-mediated mRNA decay (NMD) pathway clears eukaryotic cells of mRNAs containing premature termination codons (PTCs) or normal stop codons located in specific contexts. It therefore plays an important role in gene expression regulation. The precise molecular mechanism of the NMD pathway has long been considered to differ substantially from yeast to metazoa, despite the involvement of universally conserved factors such as the central ATP-dependent RNA-helicase Upf1. Here, we describe the crystal structure of the yeast Upf1 bound to its recently identified but yet uncharacterized partner Nmd4, show that Nmd4 stimulates Upf1 ATPase activity and that this interaction contributes to the elimination of NMD substrates. We also demonstrate that a region of Nmd4 critical for the interaction with Upf1 in yeast is conserved in the metazoan SMG6 protein, another major NMD factor. We show that this conserved region is involved in the interaction of SMG6 with UPF1 and that mutations in this region affect the levels of endogenous human NMD substrates. Our results support the universal conservation of the NMD mechanism in eukaryotes.https://doi.org/10.1371/journal.pbio.3002821 |
| spellingShingle | Irène Barbarin-Bocahu Nathalie Ulryck Amandine Rigobert Nadia Ruiz Gutierrez Laurence Decourty Mouna Raji Bhumika Garkhal Hervé Le Hir Cosmin Saveanu Marc Graille Structure of the Nmd4-Upf1 complex supports conservation of the nonsense-mediated mRNA decay pathway between yeast and humans. PLoS Biology |
| title | Structure of the Nmd4-Upf1 complex supports conservation of the nonsense-mediated mRNA decay pathway between yeast and humans. |
| title_full | Structure of the Nmd4-Upf1 complex supports conservation of the nonsense-mediated mRNA decay pathway between yeast and humans. |
| title_fullStr | Structure of the Nmd4-Upf1 complex supports conservation of the nonsense-mediated mRNA decay pathway between yeast and humans. |
| title_full_unstemmed | Structure of the Nmd4-Upf1 complex supports conservation of the nonsense-mediated mRNA decay pathway between yeast and humans. |
| title_short | Structure of the Nmd4-Upf1 complex supports conservation of the nonsense-mediated mRNA decay pathway between yeast and humans. |
| title_sort | structure of the nmd4 upf1 complex supports conservation of the nonsense mediated mrna decay pathway between yeast and humans |
| url | https://doi.org/10.1371/journal.pbio.3002821 |
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