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-Structure paper
タイトル | EDF1 coordinates cellular responses to ribosome collisions. |
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ジャーナル・号・ページ | Elife, Vol. 9, Year 2020 |
掲載日 | 2020年8月3日 |
著者 | Niladri K Sinha / Alban Ordureau / Katharina Best / James A Saba / Boris Zinshteyn / Elayanambi Sundaramoorthy / Amit Fulzele / Danielle M Garshott / Timo Denk / Matthias Thoms / Joao A Paulo / J Wade Harper / Eric J Bennett / Roland Beckmann / Rachel Green / |
PubMed 要旨 | Translation of aberrant mRNAs induces ribosomal collisions, thereby triggering pathways for mRNA and nascent peptide degradation and ribosomal rescue. Here we use sucrose gradient fractionation ...Translation of aberrant mRNAs induces ribosomal collisions, thereby triggering pathways for mRNA and nascent peptide degradation and ribosomal rescue. Here we use sucrose gradient fractionation combined with quantitative proteomics to systematically identify proteins associated with collided ribosomes. This approach identified Endothelial differentiation-related factor 1 (EDF1) as a novel protein recruited to collided ribosomes during translational distress. Cryo-electron microscopic analyses of EDF1 and its yeast homolog Mbf1 revealed a conserved 40S ribosomal subunit binding site at the mRNA entry channel near the collision interface. EDF1 recruits the translational repressors GIGYF2 and EIF4E2 to collided ribosomes to initiate a negative-feedback loop that prevents new ribosomes from translating defective mRNAs. Further, EDF1 regulates an immediate-early transcriptional response to ribosomal collisions. Our results uncover mechanisms through which EDF1 coordinates multiple responses of the ribosome-mediated quality control pathway and provide novel insights into the intersection of ribosome-mediated quality control with global transcriptional regulation. |
リンク | Elife / PubMed:32744497 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.9 - 3.0 Å |
構造データ | EMDB-11456, PDB-6zvh: EMDB-11457, PDB-6zvi: |
化合物 | ChemComp-MG: ChemComp-ZN: |
由来 |
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キーワード | RIBOSOME / translation / frameshifting / collision |