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| Status |
Public on Aug 10, 2018 |
| Title |
Ssd1 and Gcn2 suppress global translational efficiency in replicatively aged yeast, while their activation in young cells extends lifespan |
| Organism |
Saccharomyces cerevisiae |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Using ribosome profiling, we find globally reduced translation efficiency during mitotic / replicative aging in budding yeast. Two mechanisms contribute to this: Firstly, the mRNA binding protein Ssd1 is induced during aging, sequestering mRNAs to P-bodies and stress granules that are abundant in old cells. Indeed, overexpression of Ssd1 reduced protein synthesis in young cells and extended lifespan, while loss of Ssd1 reduced the translational deficit of old cells and shortened lifespan. Secondly, the Gcn2 kinase is activated in old cells, phosphorylating and inactivating the translational initiation factor eIF2α. Accordingly, deletion of GCN2 reduced the translational defect of old cells. Furthermore, overexpressing an uncharged tRNA to fully activate Gcn2, or overexpression of its downstream mediator, Gcn4, extended replicative lifespan in a manner that was mostly dependent on autophagy without inhibiting the TOR pathway. As such, Ssd1 induction, activation of the integrated stress response or autophagy are favorable TOR-independent therapeutic targets for lifespan extension.
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| Overall design |
Examination of transcription and translational efficiency in replicative lifespan analysis with RNA-seq and Ribo-seq with 3 replicates at 3 different timepoints
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| Contributor(s) |
Hu Z, Tomoiaga AS, Xia B, Chen K, Tyler JK |
| Citation(s) |
30117416 |
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| Submission date |
Oct 02, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Bo Xia |
| E-mail(s) |
bxia@houstonmethodist.org
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| Phone |
7134419140
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| Organization name |
Houston Methodist
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| Lab |
Kaifu Chen Lab
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| Street address |
6670 Bertner Ave, R10-414D
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| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
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| Platforms (1) |
| GPL13821 |
Illumina HiSeq 2000 (Saccharomyces cerevisiae) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA412874 |
| SRA |
SRP119264 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE104506_RAW.tar |
623.7 Mb |
(http)(custom) |
TAR (of WIG) |
| GSE104506_all_sample_normalized.xls.gz |
1.0 Mb |
(ftp)(http) |
XLS |
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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