PXD020239

PXD020239 is an original dataset announced via ProteomeXchange.

Title	Ribosome collisions trigger cis-acting feedback inhibition of translation initiation
Description	Translation of aberrant mRNAs can cause ribosomes to stall, leading to collisions with trailing ribosomes. Collided ribosomes are specifically recognized by ZNF598 to initiate protein and mRNA quality control pathways. Here we found using quantitative proteomics of collided ribosomes that EDF1 is a ZNF598-independent sensor of ribosome collisions. EDF1 recruits and stabilizes GIGYF2 at collisions to inhibit translation initiation in cis via 4EHP. The GIGYF2 axis acts independently of the ZNF598 axis, but each pathway’s output is more pronounced without the other. We propose that the widely conserved and highly abundant EDF1 monitors the transcriptome for excessive ribosome density, then triggers a GIGYF2-mediated response to locally and temporarily reduce ribosome loading. Only when collisions persist is translation abandoned to initiate ZNF598-dependent quality control. This tiered response to ribosome collisions would allow cells to dynamically tune translation rates while ensuring fidelity of the resulting protein products.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:09:12.193.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sew Peak-Chew
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-07 08:05:03	ID requested
1	2020-07-16 03:49:07	announced
⏵ 2	2024-10-22 05:09:15	announced	2024-10-22: Updated project metadata.

Juszkiewicz S, Slodkowicz G, Lin Z, Freire-Pritchett P, Peak-Chew SY, Hegde RS, Ribosome collisions trigger cis-acting feedback inhibition of translation initiation. Elife, 9():(2020) [pubmed]

10.7554/elife.60038;

submitter keyword: Human, ribosome stalling, quality control

Ramanujan S. Hegde
contact affiliation	MRC Laboratory of Molecular Biology, Cell Biology Division
contact email	rhegde@mrc-lmb.cam.ac.uk
lab head
Sew Peak-Chew
contact affiliation	MRC-LMB
contact email	spc@mrc-lmb.cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020239
     1. Label: PRIDE project
     2. Name: Ribosome collisions trigger cis-acting feedback inhibition of translation initiation