Ribosome collisions trigger cis-acting feedback inhibition of translation initiation
Translation of aberrant mRNAs can cause ribosomes to stall, leading to collisions with trailing ribosomes. Collided ribosomes are specifically recognised by ZNF598 to initiate protein and mRNA quality control pathways. Here we found using quantitative proteomics of collided ribosomes that EDF1 is a...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/60038 |
| _version_ | 1811199737909477376 |
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| author | Szymon Juszkiewicz Greg Slodkowicz Zhewang Lin Paula Freire-Pritchett Sew-Yeu Peak-Chew Ramanujan S Hegde |
| author_facet | Szymon Juszkiewicz Greg Slodkowicz Zhewang Lin Paula Freire-Pritchett Sew-Yeu Peak-Chew Ramanujan S Hegde |
| author_sort | Szymon Juszkiewicz |
| collection | DOAJ |
| description | Translation of aberrant mRNAs can cause ribosomes to stall, leading to collisions with trailing ribosomes. Collided ribosomes are specifically recognised by ZNF598 to initiate protein and mRNA quality control pathways. Here we found using quantitative proteomics of collided ribosomes that EDF1 is a ZNF598-independent sensor of ribosome collisions. EDF1 stabilises GIGYF2 at collisions to inhibit translation initiation in cis via 4EHP. The GIGYF2 axis acts independently of the ZNF598 axis, but each pathway’s output is more pronounced without the other. We propose that the widely conserved and highly abundant EDF1 monitors the transcriptome for excessive ribosome density, then triggers a GIGYF2-mediated response to locally and temporarily reduce ribosome loading. Only when collisions persist is translation abandoned to initiate ZNF598-dependent quality control. This tiered response to ribosome collisions would allow cells to dynamically tune translation rates while ensuring fidelity of the resulting protein products. |
| first_indexed | 2024-04-12T01:52:24Z |
| format | Article |
| id | doaj.art-25320fe37bca42ca940a58711529e988 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:52:24Z |
| publishDate | 2020-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-25320fe37bca42ca940a58711529e9882022-12-22T03:52:53ZengeLife Sciences Publications LtdeLife2050-084X2020-07-01910.7554/eLife.60038Ribosome collisions trigger cis-acting feedback inhibition of translation initiationSzymon Juszkiewicz0https://orcid.org/0000-0002-3361-7264Greg Slodkowicz1https://orcid.org/0000-0001-6918-0386Zhewang Lin2Paula Freire-Pritchett3Sew-Yeu Peak-Chew4Ramanujan S Hegde5https://orcid.org/0000-0001-8338-852XMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United KingdomMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United KingdomMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United KingdomMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United KingdomMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United KingdomMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United KingdomTranslation of aberrant mRNAs can cause ribosomes to stall, leading to collisions with trailing ribosomes. Collided ribosomes are specifically recognised by ZNF598 to initiate protein and mRNA quality control pathways. Here we found using quantitative proteomics of collided ribosomes that EDF1 is a ZNF598-independent sensor of ribosome collisions. EDF1 stabilises GIGYF2 at collisions to inhibit translation initiation in cis via 4EHP. The GIGYF2 axis acts independently of the ZNF598 axis, but each pathway’s output is more pronounced without the other. We propose that the widely conserved and highly abundant EDF1 monitors the transcriptome for excessive ribosome density, then triggers a GIGYF2-mediated response to locally and temporarily reduce ribosome loading. Only when collisions persist is translation abandoned to initiate ZNF598-dependent quality control. This tiered response to ribosome collisions would allow cells to dynamically tune translation rates while ensuring fidelity of the resulting protein products.https://elifesciences.org/articles/60038translationribosomequality control |
| spellingShingle | Szymon Juszkiewicz Greg Slodkowicz Zhewang Lin Paula Freire-Pritchett Sew-Yeu Peak-Chew Ramanujan S Hegde Ribosome collisions trigger cis-acting feedback inhibition of translation initiation eLife translation ribosome quality control |
| title | Ribosome collisions trigger cis-acting feedback inhibition of translation initiation |
| title_full | Ribosome collisions trigger cis-acting feedback inhibition of translation initiation |
| title_fullStr | Ribosome collisions trigger cis-acting feedback inhibition of translation initiation |
| title_full_unstemmed | Ribosome collisions trigger cis-acting feedback inhibition of translation initiation |
| title_short | Ribosome collisions trigger cis-acting feedback inhibition of translation initiation |
| title_sort | ribosome collisions trigger cis acting feedback inhibition of translation initiation |
| topic | translation ribosome quality control |
| url | https://elifesciences.org/articles/60038 |
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