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| Status |
Public on Dec 02, 2023 |
| Title |
Nuclear release of eIF1 restricts start-codon selection during mitosis |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Regulated start-codon selection has the potential to reshape the proteome through the differential production of upstream open reading frames, 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 enhanced stringency of start-codon selection during mitosis results from increased association between the 40S ribosome and the key regulator of start-codon selection, eIF1. We find that increased eIF1–40S ribosome interaction during mitosis is mediated by the release of a nuclear pool of eIF1 upon nuclear envelope breakdown. Selectively depleting the nuclear pool of eIF1 eliminates the change to translational stringency during mitosis, resulting in 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 chemotherapies. Thus, cells globally control stringency of translation initiation, which has critical roles during the mammalian cell cycle in preserving mitotic cell physiology.
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| Overall design |
Paired translation initiation site profiling, elongating ribosome profiling, and RNA sequencing data for synchronized interphase, mitotic arrested, and cycling mitotic HeLa cells. Biological replicates were defined as separate cell synchronization, lysate preparation, and fractionation. N=2 biological replicates were performed each cell cycle stage.
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| Web link |
https://www.nature.com/articles/s41586-024-08088-3
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| Contributor(s) |
Ly J, Xiang K, Bartel DP, Cheeseman IM |
| Citation(s) |
39443796 |
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| Submission date |
Apr 20, 2023 |
| Last update date |
Nov 21, 2024 |
| Contact name |
Jimmy Ly |
| Organization name |
Whitehead Institute
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| Department |
Biology
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| Lab |
Iain Cheeseman
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| Street address |
455 main street
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| City |
Cambridge |
| State/province |
Massachusetts |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA957808 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE230189_CellCycle_ORF_input_counts.txt.gz |
329.0 Kb |
(ftp)(http) |
TXT |
| GSE230189_CellCycle_TIS_input_counts.txt.gz |
281.5 Kb |
(ftp)(http) |
TXT |
| GSE230189_RAW.tar |
510.0 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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