title: RACK1 is a ribosome scaffold protein for β-actin mRNA/ZBP1 complex.
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.
authors.affiliation: European Brain Research Institute (EBRI), Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Ceci
authors.forename: Kristy
authors.initials: K
authors.lastname: Welshhans
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ciotti
authors.forename: Rossella
authors.initials: R
authors.lastname: Brandi
authors.forename: Chiara
authors.initials: C
authors.lastname: Parisi
authors.forename: Francesca
authors.initials: F
authors.lastname: Paoletti
authors.forename: Luana
authors.initials: L
authors.lastname: Pistillo
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Bassell
authors.forename: Antonino
authors.initials: A
authors.lastname: Cattaneo
mesh_terms: D000199:Actins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000199:Actins; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C485731:ZBP1 protein, human; D019204:GTP-Binding Proteins