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Uncharged tRNAGln as an indicator of intracellular amino acid level upregulates UBC expression to maintain its charging level

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE188862 | GEO | 2022/11/30

REPOSITORIES: GEO

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Uncharged tRNAGln as an indicator of intracellular amino acid level upregulates UBC expression to maintain its charging level VI

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Translation in amino-acid-poor environments is limited by tRNAGln charging.

Project description: Not available

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Translation in amino acid-poor environments is limited by tRNAGln charging

Project description: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 the key sensors of glutamine availability in mammalian cells.

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Project description: Not available

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