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GCN2 suppresses TOP mRNA translation via LARP1

ABSTRACT: La-related protein 1 (LARP1) has been identified as a key translational inhibitor of terminal oligopyrimidine tract (TOP) mRNAs downstream of the nutrient sensing protein kinase complex, mTORC1. LARP1 exerts this inhibitory effect on TOP mRNA translation by binding to the mRNA cap and the adjacent 5’TOP motif, resulting in the displacement of the eIF4E complex from TOP mRNAs. In the present study, we identify a second nutrient sensing kinase GCN2 that converges on LARP1 to control TOP mRNA translation. GCN2 inhibits TOP mRNA translation via ATF4-dependent transcriptional induction of LARP1 mRNAs and GCN1-mediated recruitment of LARP1 to stalled ribosomes. We performed ATF4 ChIP-seq experiments in both WT and GCN2 KO MEFs with or without leucine deprivation.

ORGANISM(S): Mus musculus

PROVIDER: GSE166590 | GEO | 2022/08/31

REPOSITORIES: GEO

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GCN2 suppresses TOP mRNA translation via LARP1

Project description:GCN2 suppresses TOP mRNA translation via LARP1

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