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Nuclear release of eIF1 globally increases translation initiation stringency during mitosis

ABSTRACT: Regulated translation initiation has the potential to reshape the proteome, but conditions under which start codon selection is altered remain poorly defined. Here, using global translation initiation site profiling, we reveal widespread changes in start codon selection during the mammalian cell cycle. Low-efficiency initiation sites are preferentially repressed in mitosis, resulting in changes in the relative translation of thousands of annotated proteins, alternative translational isoforms, and uORFs. This increased mitotic translational stringency results from the cytoplasmic release of a nuclear pool of eIF1 upon nuclear envelope breakdown. Increased eIF1-40S ribosome interactions repress suboptimal initiation sites to rewire the mitotic proteome. Selectively depleting the nuclear pool of eIF1 eliminates changes to translational stringency during mitosis, resulting in substantially increased cell death following an extended mitotic delay induced by anti-mitotic chemotherapeutics. Thus, cells globally control translation initiation stringency to alter their physiology with critical roles during the mammalian cell cycle.

ORGANISM(S): Homo sapiens

PROVIDER: GSE230189 | GEO | 2023/12/02

REPOSITORIES: GEO

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