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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

Project description:We profiled the cellular tRNA charging landscape using next-generation sequencing and identified a subset of tRNA that sense nutrients. The charging levels of tRNAGln were exclusively and significantly decreased in response to amino acid starvation.

2022-11-30 | GSE188861 | GEO

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

2022-11-30 | GSE188860 | GEO

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

2022-11-30 | GSE188859 | GEO

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

2022-11-30 | GSE188858 | GEO

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

2022-11-30 | GSE188857 | GEO

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

2022-11-30 | GSE188855 | GEO

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 key sensors of glutamine availability in mammalian cells.

| S-EPMC7744096 | biostudies-literature

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.

2020-12-14 | GSE157276 | GEO

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

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

| PRJNA660742 | ENA

Selective charging of tRNA isoacceptors induced by amino-acid starvation.

Project description:Aminoacylated (charged) transfer RNA isoacceptors read different messenger RNA codons for the same amino acid. The concentration of an isoacceptor and its charged fraction are principal determinants of the translation rate of its codons. A recent theoretical model predicts that amino-acid starvation results in 'selective charging' where the charging levels of some tRNA isoacceptors will be low and those of others will remain high. Here, we developed a microarray for the analysis of charged fractions of tRNAs and measured charging for all Escherichia coli tRNAs before and during leucine, threonine or arginine starvation. Before starvation, most tRNAs were fully charged. During starvation, the isoacceptors in the leucine, threonine or arginine families showed selective charging when cells were starved for their cognate amino acid, directly confirming the theoretical prediction. Codons read by isoacceptors that retain high charging can be used for efficient translation of genes that are essential during amino-acid starvation. Selective charging can explain anomalous patterns of codon usage in the genes for different families of proteins.

| S-EPMC1299251 | biostudies-literature

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