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TitleEDF1 coordinates cellular responses to ribosome collisions.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateAug 3, 2020
AuthorsNiladri 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 AbstractTranslation 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.
External linksElife / PubMed:32744497 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.0 Å
Structure data

11456

6zvh

EMDB-11456, PDB-6zvh:
EDF1-ribosome complex
Method: EM (single particle) / Resolution: 2.9 Å

11457

6zvi

EMDB-11457, PDB-6zvi:
Mbf1-ribosome complex
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsRIBOSOME / translation / frameshifting / collision

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