Translation in amino-acid-poor environments is limited by tRNA(Gln) charging Journal Article
| Authors: | Pavlova, N. N.; King, B.; Josselsohn, R. H.; Violante, S.; Macera, V. L.; Vardhana, S. A.; Cross, J. R.; Thompson, C. B. |
| Article Title: | Translation in amino-acid-poor environments is limited by tRNA(Gln) charging |
| Abstract: | An inadequate supply of amino acids leads to accumulation of uncharged tRNAs, which can bind and activate GCN2 kinase to reduce translation. Here, we show that glutamine-specific tRNAs selectively become uncharged when extracellular amino acid availability is compromised. In contrast, all other tRNAs retain charging of their cognate amino acids in a manner that is dependent upon intact lysosomal function. In addition to GCN2 activation and reduced total translation, the reduced charging of tRNAGln in amino-acid-deprived cells also leads to specific depletion of proteins containing polyglutamine tracts including core-binding factor α1, mediator subunit 12, transcriptional coactivator CBP and TATA-box binding protein. Treating amino-acid-deprived cells with exogenous glutamine or glutaminase inhibitors restores tRNAGln charging and the levels of polyglutamine-containing proteins. Together, these results demonstrate that the activation of GCN2 and the translation of polyglutamine-encoding transcripts serve as key sensors of glutamine availability in mammalian cells. © 2020, Pavlova et al. |
| Keywords: | mouse; translation; glutamine; trna; cell biology; polyglutamine; human; nutrient depletion |
| Journal Title: | eLife |
| Volume: | 9 |
| ISSN: | 2050-084X |
| Publisher: | eLife Sciences Publications Ltd. |
| Date Published: | 2020-12-08 |
| Start Page: | e62307 |
| Language: | English |
| DOI: | 10.7554/eLife.62307 |
| PUBMED: | 33289483 |
| PROVIDER: | scopus |
| PMCID: | PMC7744096 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2021 -- Source: Scopus |
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