PXD054183-1

PXD054183 is an original dataset announced via ProteomeXchange.

Title	Nuclear release of eIF1 globally increases stringency of start codon selection to preserve mitotic arrest physiology
Description	Regulated start codon selection has the potential to reshape the proteome through the differential production of uORFs, canonical proteins, and alternative translational isoforms. However, conditions under which start codon selection is altered remain poorly defined. Here, using transcriptome-wide translation initiation site profiling, we reveal a global increase in the stringency of start codon selection during mammalian mitosis. Low-efficiency initiation sites are preferentially repressed in mitosis, resulting in pervasive changes in the translation of thousands of start sites and their corresponding protein products. This increased stringency of start codon selection during mitosis results from increased associations between the 40S ribosome and the key regulator of start codon selection, eIF1. We find that increased eIF1-40S ribosome interactions during mitosis are mediated by the release of a nuclear pool of eIF1 upon nuclear envelope breakdown. Selectively depleting the nuclear pool of eIF1 eliminates the changes to translational stringency during mitosis, resulting in the altered synthesis of thousands of protein isoforms. In addition, preventing mitotic translational rewiring results in substantially increased cell death and decreased mitotic slippage in cells that experience a mitotic delay induced by anti-mitotic chemotherapeutics. Thus, cells globally control translation initiation stringency with critical roles during the mammalian cell cycle to preserve mitotic cell physiology.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_10:52:04.877.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD054183
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jimmy Ly
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-24 08:09:40	ID requested
⏵ 1	2024-10-07 10:52:05	announced
2	2024-10-22 07:00:51	announced	2024-10-22: Updated project metadata.

10.1101/2024.04.06.588385;

Ly J, Xiang K, Su KC, Sissoko GB, Bartel DP, Cheeseman IM, Nuclear release of eIF1 globally increases stringency of start-codon selection to preserve mitotic arrest physiology. bioRxiv, ():(2024) [pubmed]

10.6019/PXD054183;

submitter keyword: Translation, ribosomes, mitosis, cell cycle

Iain Cheeseman
contact affiliation	Whitehead Institute and MIT
contact email	icheese@wi.mit.edu
lab head
Jimmy Ly
contact affiliation	PhD student
contact email	jimmyly@wi.mit.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054183
     1. Label: PRIDE project
     2. Name: Nuclear release of eIF1 globally increases stringency of start codon selection to preserve mitotic arrest physiology