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| Status |
Public on Jun 09, 2023 |
| Title |
Nuclear translocation of an aminoacyl-tRNA synthetase may mediate a chronic "integrated stress response" |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Various stress conditions are signaled through phosphorylation of translation initiation factor eukaryotic initiation factor 2α (eIF2α) to inhibit global translation while selectively activating transcription factor ATF4 to aid cell survival and recovery. However, this integrated stress response is acute and cannot resolve lasting stress. Here, we report that tyrosyl-tRNA synthetase (TyrRS), a member of the aminoacyl-tRNA synthetase family that responds to diverse stress conditions through cytosol-nucleus translocation to activate stress-response genes, also inhibits global translation. However, it occurs at a later stage than eIF2α/ATF4 and mammalian target of rapamycin (mTOR) responses. Excluding TyrRS from the nucleus over-activates translation and increases apoptosis in cells under prolonged oxidative stress. Nuclear TyrRS transcriptionally represses translation genes by recruiting TRIM28 and/or NuRD complex. We propose that TyrRS, possibly along with other family members, can sense a variety of stress signals through intrinsic properties of this enzyme and strategically located nuclear localization signal and integrate them by nucleus translocation to effect protective responses against chronic stress.
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| |
|
| Overall design |
Tyrosyl-tRNA synthetase DNA binding sites (TF-ChIP)
|
| Web link |
https://www.sciencedirect.com/science/article/pii/S2211124723006435?via%3Dihub
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| |
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| Contributor(s) |
Wei N, Yang X, Cui H |
| Citation(s) |
37314928 |
| |
| Submission date |
Jul 28, 2020 |
| Last update date |
Sep 08, 2023 |
| Contact name |
Xiang-Lei Yang |
| E-mail(s) |
xlyang@scripps.edu
|
| Phone |
8587848976
|
| Organization name |
Scripps Research
|
| Department |
Molecular Medicine
|
| Lab |
Yang
|
| Street address |
10550 North Torrey Pines Road BCC-110
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA649280 |
| SRA |
SRP274003 |
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