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

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

PROVIDER: PRJNA975195 | ENA |

REPOSITORIES: ENA

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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.

2024-01-15 | GSE233183 | GEO

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

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

| PRJNA975193 | ENA

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.

2024-01-15 | GSE233182 | GEO

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

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

| PRJNA975192 | ENA

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

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

2024-01-15 | GSE233186 | GEO

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

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

| PRJNA975198 | ENA

The LARP1 homolog Slr1p controls the stability and expression of proto-5’TOP mRNAs in fission yeast [RIP-seq]

Project description:Messenger RNAs (mRNAs) in higher eukaryotes that encode highly expressed proteins important for the assembly of the translational apparatus (e.g. ribosomal proteins) often harbour a pyrimidine-rich motif at the extreme 5’ end known as a 5’ terminal oligopyrimidine (5’TOP) sequence. Members of the La-related protein 1 (LARP1) family control 5’TOP expression through a conserved DM15 motif, but the mechanism is not well understood. 5’TOP motifs have not been described in many lower organisms, but fission yeast (and many other single-celled eukaryotes) harbour a LARP1 homolog that also lacks a DM15 motif. In this work, we show that the fission yeast LARP1 homolog, Slr1p, controls the translation and stability of mRNAs encoding proteins analogous to 5’TOP mRNAs in higher eukaryotes, which we thus refer to as proto-5’TOPs. Our data suggest that the LARP1 DM15 motif and the mRNA 5’TOP motif may be features that were scaffolded over a more fundamental mechanism of LARP1 family member-associated control of gene expression that is still utilized in lower systems.

2023-07-18 | GSE237526 | GEO

The LARP1 homolog Slr1p controls the stability and expression of proto-5’TOP mRNAs in fission yeast [RNA-seq]

2023-07-21 | GSE237860 | GEO

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

Project description:A central mechanism of mTOR complex 1 (mTORC1) signaling is the coordinated translation of ribosomal protein and translation factor mRNAs mediated by the 5'-terminal oligopyrimidine motif (5'TOP). Recently, La-related protein 1 (LARP1) was proposed to be the specific regulator of 5'TOP mRNA translation downstream of mTORC1, while eIF4E-binding proteins (4EBP1/2) were suggested to have a general role in translational repression of all transcripts. Here, we use single-molecule translation site imaging of 5'TOP and canonical mRNAs to study the translation of single mRNAs in living cells. Our data reveal that 4EBP1/2 has a dominant role in repression of translation of both 5'TOP and canonical mRNAs during pharmacological inhibition of mTOR. In contrast, we find that LARP1 selectively protects 5'TOP mRNAs from degradation in a transcriptome-wide analysis of mRNA half-lives. Our results clarify the roles of 4EBP1/2 and LARP1 in regulating 5'TOP mRNAs and provide a framework to further study how these factors control cell growth during development and disease.

| S-EPMC10871529 | biostudies-literature

GCN2 suppresses TOP mRNA translation via LARP1

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.

2022-08-31 | GSE166590 | GEO

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