title: Two isoforms of the cold-inducible mRNA-binding protein RBM3 localize to dendrites and promote translation.
abstract: A diverse set of mRNA-binding proteins (BPs) regulate local translation in neurons. However, little is known about the role(s) played by a family of cold-inducible, glycine-rich mRNA-BPs. Unlike neuronal mRNA-BPs characterized thus far, these proteins are induced by hypothermia and are comprised of one RNA recognition motif and an adjacent arginine- and glycine-rich domain. We studied the expression and function of the RNA-binding motif protein 3 (RBM3), a member of this family, in neurons. RBM3 was expressed in multiple brain regions, with the highest levels in cerebellum and olfactory bulb. In dissociated neurons, RBM3 was observed in nuclei and in a heterogeneous population of granules within dendrites. In sucrose gradient assays, RBM3 cofractionated with heavy mRNA granules and multiple components of the translation machinery. Two alternatively spliced RBM3 isoforms that differed by a single arginine residue were identified in neurons; both were post-translationally modified. The variant lacking the spliced arginine exhibited a higher dendritic localization and was the only isoform present in astrocytes. When overexpressed in neuronal cell lines, RBM3 isoforms-enhanced global translation, the formation of active polysomes, and the activation of initiation factors. These data suggest that RBM3 plays a distinctive role in enhancing translation in neurons.
authors.affiliation: Department of Neurobiology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: Smart
authors.forename: Armaz
authors.initials: A
authors.lastname: Aschrafi
authors.forename: Annette
authors.initials: A
authors.lastname: Atkins
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Owens
authors.forename: Julie
authors.initials: J
authors.lastname: Pilotte
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Cunningham
authors.forename: Peter W
authors.initials: PW
authors.lastname: Vanderklish
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D004622:Embryo, Mammalian; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D009474:Neurons / Q000166:cytology*; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
chemical_list: D020033:Protein Isoforms; C099506:RBM3 protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins