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Regulation of protein translation during mitosis

ABSTRACT: Entry into and exit from mitosis is driven by precisely-timed changes in protein abundance, and involves transcriptional regulation and protein degradation. However, the role of translational regulation in modulating cellular protein content during mitosis remains poorly understood. Here, using ribosome profiling, we show that translational, rather than transcriptional regulation is the dominant mechanism for modulating protein synthesis at mitotic entry. The vast majority of regulated mRNAs are translationally repressed, which contrasts previous findings of selective mRNA translational activation at mitotic entry. One of the most pronounced translationally repressed genes in mitosis is Emi1, an inhibitor of the anaphase promoting complex (APC), which is degraded during mitosis. We show that Emi1 degradation is insufficient for full APC activation and that simultaneous translational repression is required. These results provide a genome-wide view of protein translation during mitosis and suggest that translational repression may be used to ensure complete protein inactivation

ORGANISM(S): Homo sapiens

PROVIDER: GSE67902 | GEO | 2015/09/01

SECONDARY ACCESSION(S): PRJNA281177

REPOSITORIES: GEO

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Regulation of protein translation during mitosis

Project description:Entry into and exit from mitosis is driven by precisely-timed changes in protein abundance, and involves transcriptional regulation and protein degradation. However, the role of translational regulation in modulating cellular protein content during mitosis remains poorly understood. Here, using ribosome profiling, we show that translational, rather than transcriptional regulation is the dominant mechanism for modulating protein synthesis at mitotic entry. The vast majority of regulated mRNAs are translationally repressed, which contrasts previous findings of selective mRNA translational activation at mitotic entry. One of the most pronounced translationally repressed genes in mitosis is Emi1, an inhibitor of the anaphase promoting complex (APC), which is degraded during mitosis. We show that Emi1 degradation is insufficient for full APC activation and that simultaneous translational repression is required. These results provide a genome-wide view of protein translation during mitosis and suggest that translational repression may be used to ensure complete protein inactivation Ribosome profiling and mRNA-seq from 3 time points in the cell cycle

2015-09-01 | E-GEOD-67902 | biostudies-arrayexpress

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Nuclear release of eIF1 globally increases stringency of start codon selection to preserve mitotic arrest physiology

Project 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.

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