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TitleMechanism of ribosome-associated mRNA degradation during tubulin autoregulation.
Journal, issue, pagesMol Cell, Vol. 83, Issue 13, Page 2290-2302.e13, Year 2023
Publish dateJul 6, 2023
AuthorsMarkus Höpfler / Eva Absmeier / Sew-Yeu Peak-Chew / Evangelia Vartholomaiou / Lori A Passmore / Ivana Gasic / Ramanujan S Hegde /
PubMed AbstractMicrotubules play crucial roles in cellular architecture, intracellular transport, and mitosis. The availability of free tubulin subunits affects polymerization dynamics and microtubule function. ...Microtubules play crucial roles in cellular architecture, intracellular transport, and mitosis. The availability of free tubulin subunits affects polymerization dynamics and microtubule function. When cells sense excess free tubulin, they trigger degradation of the encoding mRNAs, which requires recognition of the nascent polypeptide by the tubulin-specific ribosome-binding factor TTC5. How TTC5 initiates the decay of tubulin mRNAs is unknown. Here, our biochemical and structural analysis reveals that TTC5 recruits the poorly studied protein SCAPER to the ribosome. SCAPER, in turn, engages the CCR4-NOT deadenylase complex through its CNOT11 subunit to trigger tubulin mRNA decay. SCAPER mutants that cause intellectual disability and retinitis pigmentosa in humans are impaired in CCR4-NOT recruitment, tubulin mRNA degradation, and microtubule-dependent chromosome segregation. Our findings demonstrate how recognition of a nascent polypeptide on the ribosome is physically linked to mRNA decay factors via a relay of protein-protein interactions, providing a paradigm for specificity in cytoplasmic gene regulation.
External linksMol Cell / PubMed:37295431 / PubMed Central
MethodsEM (single particle)
Resolution2.8 Å
Structure data

16155

8bpo

EMDB-16155, PDB-8bpo:
Structure of rabbit 80S ribosome translating beta-tubulin in complex with tetratricopeptide protein 5 (TTC5) and S-phase Cyclin A Associated Protein residing in the ER (SCAPER)
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • oryctolagus cuniculus (rabbit)
  • rabbit (rabbit)
  • homo sapiens (human)
KeywordsRIBOSOME / tubulin auto-regulation mRNA decay translation SCAPER

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