title: Dual nature of translational control by regulatory BC RNAs.
abstract: In higher eukaryotes, increasing evidence suggests, gene expression is to a large degree controlled by RNA. Regulatory RNAs have been implicated in the management of neuronal function and plasticity in mammalian brains. However, much of the molecular-mechanistic framework that enables neuronal regulatory RNAs to control gene expression remains poorly understood. Here, we establish molecular mechanisms that underlie the regulatory capacity of neuronal BC RNAs in the translational control of gene expression. We report that regulatory BC RNAs employ a two-pronged approach in translational control. One of two distinct repression mechanisms is mediated by C-loop motifs in BC RNA 3' stem-loop domains. These C-loops bind to eIF4B and prevent the factor's interaction with 18S rRNA of the small ribosomal subunit. In the second mechanism, the central A-rich domains of BC RNAs target eIF4A, specifically inhibiting its RNA helicase activity. Thus, BC RNAs repress translation initiation in a bimodal mechanistic approach. As BC RNA functionality has evolved independently in rodent and primate lineages, our data suggest that BC RNA translational control was necessitated and implemented during mammalian phylogenetic development of complex neural systems.
authors.affiliation: The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, State University of New York, Health Science Center at Brooklyn, Brooklyn, New York 11203, USA.
authors.forename: Taesun
authors.initials: T
authors.lastname: Eom
authors.forename: Valerio
authors.initials: V
authors.lastname: Berardi
authors.forename: Jun
authors.initials: J
authors.lastname: Zhong
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Risuleo
authors.forename: Henri
authors.initials: H
authors.lastname: Tiedge
mesh_terms: D000818:Animals; D001483:Base Sequence; D039601:Eukaryotic Initiation Factor-4A / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D055029:Inverted Repeat Sequences; D051379:Mice; D009474:Neurons / Q000378:metabolism; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D012337:RNA, Ribosomal, 18S / Q000235:genetics / Q000378:metabolism; D020733:RNA, Small Cytoplasmic / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D054679:Ribosome Subunits, Small / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: D039642:Eukaryotic Initiation Factors; D012337:RNA, Ribosomal, 18S; D020733:RNA, Small Cytoplasmic; D011994:Recombinant Proteins; C031799:eIF-4B; D012313:RNA; D039601:Eukaryotic Initiation Factor-4A