PXD041096

PXD041096 is an original dataset announced via ProteomeXchange.

Title	Mechanism of ribosome-associated mRNA degradation during tubulin autoregulation
Description	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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:01:49.502.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Markus Hoepfler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-24 06:50:03	ID requested
1	2023-07-03 02:52:13	announced
⏵ 2	2023-11-14 09:01:57	announced	2023-11-14: Updated project metadata.

H, ö, pfler M, Absmeier E, Peak-Chew SY, Vartholomaiou E, Passmore LA, Gasic I, Hegde RS, Mechanism of ribosome-associated mRNA degradation during tubulin autoregulation. Mol Cell, 83(13):2290-2302.e13(2023) [pubmed]

submitter keyword: Orbitrap Eclipse, Q Exactive Plus,Human LC-MS/MS

Ramanujan S. Hegde
contact affiliation	MRC Laboratory of Molecular Biology
contact email	rhegde@mrc-lmb.cam.ac.uk
lab head
Markus Hoepfler
contact affiliation	MRC Laboratory of Molecular Biology
contact email	mhoepfler@mrc-lmb.cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041096
     1. Label: PRIDE project
     2. Name: Mechanism of ribosome-associated mRNA degradation during tubulin autoregulation