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Distinct roles of LARP1 and 4EBP1/2 in regulating translation and stability of 5′TOP mRNAs

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE233187 | GEO | 2024/01/15

REPOSITORIES: GEO

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Distinct roles of LARP1 and 4EBP1/2 in regulating translation and stability of 5′TOP mRNAs [LARP1]

Project description:To investigate the changes in gene expression upon loss of LARP1, we performed RNA-seq and differential gene expression analysis on WT and derived LARP1 KO cell lines. The canonical and 5′TOP mRNA cell lines used for single-molecule imaging were treated as biological replicates for the differential gene expression analysis.

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Distinct roles of LARP1 and 4EBP1/2 in regulating translation and stability of 5′TOP mRNAs [4EBP1/2]

Project description:To investigate the changes in gene expression upon loss of 4EBP1/2, we performed RNA-seq and differential gene expression analysis on WT and derived 4EBP1/2 KD cell lines. The canonical and 5′TOP mRNA cell lines used for single-molecule imaging were treated as biological replicates for the differential gene expression analysis.

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Distinct roles of LARP1 and 4EBP1/2 in regulating translation and stability of 5′TOP mRNAs [S4U label]

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Project description: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.

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