RACK1 Is a Ribosome Scaffold Protein for beta-actin mRNA/ZBP1 Complex

• Type of Material: Article
• Authors: Marcello Ceci, European Brain Research Institute; Kristy Welshhans, Kent State University; Maria Teresa Ciotti, Institute of Neurobiology and Molecular Medicine, Italy; Rossella Brandi, European Brain Research Institute; Chiara Parisi, European Brain Research Institute; Francesca Paoletti, European Brain Research Institute; Luana Pistillo, European Brain Research Institute; Gary Bassell, Emory University; Antonino Cattaneo, European Brain Research Institute
• Language: English
• Date: 2012-04-16
• Publisher: PUBLIC LIBRARY SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Ceci et al.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0035034
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 7
• Issue: 4
• Start Page: e35034
• End Page: e35034
• Grant/Funding Information: This work is supported by grant from IIT, Technology Italian Institute (WWW.iit.it project to A. Cattaneo)
• Keywords: SUBUNIT; STRESS GRANULES; RECEPTOR; LOCALIZATION; ACTIVATED C-KINASE; SRC; DEPENDENT TRANSLATION; MULTIDISCIPLINARY SCIENCES; Multidisciplinary Sciences; MESSENGER-RNA; Science & Technology; HIPPOCAMPAL-NEURONS; Science & Technology - Other Topics; GROWTH
• Research Categories: Health Sciences, General; Biology, Cell; Biology, Molecular

Abstract

In neurons, specific mRNAs are transported in a translationally repressed manner along dendrites or axons by transport ribonucleic-protein complexes called RNA granules. ZBP1 is one RNA binding protein present in transport RNPs, where it transports and represses the translation of cotransported mRNAs, including β-actin mRNA. The release of β-actin mRNA from ZBP1 and its subsequent translation depends on the phosphorylation of ZBP1 by Src kinase, but little is known about how this process is regulated. Here we demonstrate that the ribosomal-associated protein RACK1, another substrate of Src, binds the β-actin mRNA/ZBP1 complex on ribosomes and contributes to the release of β-actin mRNA from ZBP1 and to its translation. We identify the Src binding and phosphorylation site Y246 on RACK1 as the critical site for the binding to the β-actin mRNA/ZBP1 complex. Based on these results we propose RACK1 as a ribosomal scaffold protein for specific mRNA-RBP complexes to tightly regulate the translation of specific mRNAs.