title: LARP4B is an AU-rich sequence associated factor that promotes mRNA accumulation and translation.
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.
authors.affiliation: Biozentrum Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Maritta
authors.initials: M
authors.lastname: Küspert
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, D-13092 Berlin, Germany.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Murakawa
authors.affiliation: Biozentrum Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schäffler
authors.affiliation: Rudolf-Virchow-Zentrum für Experimentelle Biomedizin, Universität Würzburg, D-97080 Würzburg, Germany.
authors.forename: Jens T
authors.initials: JT
authors.lastname: Vanselow
authors.affiliation: Biozentrum Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Wolf
authors.affiliation: Biozentrum Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Juranek
authors.affiliation: Rudolf-Virchow-Zentrum für Experimentelle Biomedizin, Universität Würzburg, D-97080 Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schlosser
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, D-13092 Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Landthaler
authors.affiliation: Biozentrum Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany Rudolf-Virchow-Zentrum für Experimentelle Biomedizin, Universität Würzburg, D-97080 Würzburg, Germany Department of Radiation Medicine and Applied Sciences, University of California at San Diego, San Diego, California 92037, USA.
authors.forename: Utz
authors.initials: U
authors.lastname: Fischer
mesh_terms: D063307:AU Rich Elements; D001324:Autoantigens / Q000737:chemistry / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000737:chemistry / Q000502:physiology*; D000097585:SS-B Antigen
chemical_list: D001324:Autoantigens; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D000097585:SS-B Antigen
keywords: La-related proteins; mRNA; mRNP code; translation