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LARP4B is an AU-rich sequence associated factor that promotes mRNA accumulation and translation

Item Type:Article
Title:LARP4B is an AU-rich sequence associated factor that promotes mRNA accumulation and translation
Creators Name:Küspert, M. and Murakawa, Y. and Schäffler, K. and Vanselow, J.T. and Wolf, E. and Juranek, S. and Schlosser, A. and Landthaler, M. and Fischer, U.
Abstract:mRNAs are key molecules in gene expression and subject to diverse regulatory events. Regulation is accomplished by distinct sets of trans-acting factors that interact with mRNAs and form defined mRNA-protein complexes (mRNPs). The resulting "mRNP code" determines the fate of any given mRNA and thus controlling gene expression at the post-transcriptional level. The La-related protein 4B (LARP4B) belongs to an evolutionarily conserved family of RNA-binding proteins characterized by the presence of a La-module implicated in direct RNA binding. Biochemical experiments have shown previously direct interactions of LARP4B with factors of the translation machinery. This finding along with the observation of an association with actively translating ribosomes suggested that LARP4B is a factor contributing to the mRNP code. To gain insight into the function of LARP4B in vivo we tested its mRNA association at the transcriptome level and its impact on the proteome. PAR-CLIP analyses allowed us to identify the in vivo RNA targets of LARP4B. We show that LARP4B binds to a distinct set of cellular mRNAs by contacting their 3' UTRs. Biocomputational analysis combined with in vitro binding assays identified the LARP4B-binding motif on mRNA targets. The reduction of cellular LARP4B levels leads to a marked destabilization of its mRNA targets and consequently their reduced translation. Our data identify LARP4B as a component of the mRNP code that influences the expression of its mRNA targets by affecting their stability.
Keywords:La-related Proteins, Translation, mRNA, mRNP Code
Publisher:Cold Spring Harbor Laboratory Press
Page Range:1294-1305
Date:July 2015
Additional Information:Copyright © 2015 Küspert et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society. This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
Official Publication:https://doi.org/10.1261/rna.051441.115
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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