Proteomics

Dataset Information

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Mechanism of ribosome-associated mRNA degradation during tubulin autoregulation


ABSTRACT: Microtubules play crucial roles in cellular architecture, intracellular transport, and mitosis. The availability of free tubulin subunits impacts 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 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.

INSTRUMENT(S): Orbitrap Eclipse, Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: Markus Hoepfler  

LAB HEAD: Ramanujan S. Hegde

PROVIDER: PXD041096 | Pride | 2023-07-03

REPOSITORIES: Pride

Dataset's files

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Action DRS
MBQ5360_TMT16_F1r.raw Raw
MBQ5360_TMT16_F2.raw Raw
MBQ5360_TMT16_F3.raw Raw
MBQ5360_TMT16_F4.raw Raw
MBQ5360_TMT16_prot_m14.txt Txt
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Publications

Mechanism of ribosome-associated mRNA degradation during tubulin autoregulation.

Höpfler Markus M   Absmeier Eva E   Peak-Chew Sew-Yeu SY   Vartholomaiou Evangelia E   Passmore Lori A LA   Gasic Ivana I   Hegde Ramanujan S RS  

Molecular cell 20230608 13


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 reveal  ...[more]

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