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Series GSE230189 Query DataSets for GSE230189
Status Public on Dec 02, 2023
Title Nuclear release of eIF1 globally increases translation initiation stringency during mitosis
Organism Homo sapiens
Experiment type Other
Summary 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. 
 
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.
 
Contributor(s) Ly J, Xiang K, Bartel DP, Cheeseman IM
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Submission date Apr 20, 2023
Last update date Dec 04, 2023
Contact name Jimmy Ly
Organization name Whitehead Institute
Department Biology
Lab Iain Cheeseman
Street address 455 main street
City Cambridge
State/province Massachusetts
ZIP/Postal code 02142
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (24)
GSM7191425 Interphase TIS RPF rep 1
GSM7191426 Interphase TIS Input RNA rep 1
GSM7191427 Interphase elongating RPF rep 1
Relations
BioProject PRJNA957808

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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 SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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