Multifunctional RNA-binding proteins influence mRNA abundance and translational efficiency of distinct sets of target genes

• Main Authors: Hubner, N. (Author), Ruiz-Orera, J. (Author), Schneider-Lunitz, V. (Author), vanHeesch, S. (Author)
• Format: Article
• Language: English
• Published: Public Library of Science 2021
• Subjects: 5' untranslated region; Article; BCLAF1 protein; binding affinity; biology; cardiac muscle; cohort analysis; Computational Biology; computer model; controlled study; cytology; DDX3X protein; DDX42 protein; DDX6 protein; DROSHA protein; EFTUD2 protein; FAM120A protein; FASTKD2 protein; G3BP1 protein; GEMIN5 protein; gene expression; gene expression regulation; Gene Expression Regulation; genetics; HNRNPM protein; human; human cell; human tissue; Humans; in vivo study; messenger RNA; metabolism; Myocardium; NKRF protein; NOLC1 protein; Protein Biosynthesis; protein synthesis; PRPF8 protein; PUM1 protein; RBM22 protein; RNA binding protein; RNA translation; RNA, Messenger; RNA-Binding Proteins; SRSF1 protein; SRSF7 protein; TRA2A protein; translation regulation; U2AF2 protein; UCHL5 protein; unclassified drug
• Online Access: View Fulltext in Publisher

 RNA-binding proteins (RBPs) can regulate more than a single aspect of RNA metabolism. We searched for such previously undiscovered multifunctionality within a set of 143 RBPs, by defining the predictive value of RBP abundance for the transcription and translation levels of known RBP target genes across 80 human hearts. This led us to newly associate 27 RBPs with cardiac translational regulation in vivo. Of these, 21 impacted both RNA expression and translation, albeit for virtually independent sets of target genes. We highlight a subset of these, including G3BP1, PUM1, UCHL5, and DDX3X, where dual regulation is achieved through differential affinity for target length, by which separate biological processes are controlled. Like the RNA helicase DDX3X, the known splicing factors EFTUD2 and PRPF8—all identified as multifunctional RBPs by our analysis—selectively influence target translation rates depending on 5’ UTR structure. Our analyses identify dozens of RBPs as being multifunctional and pinpoint potential novel regulators of translation, postulating unanticipated complexity of protein-RNA interactions at consecutive stages of gene expression. © 2021 Schneider-Lunitz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.