title: RNA diversity has profound effects on the translation of neuronal nitric oxide synthase.
abstract: A comprehensive analysis of the structure of neuronal nitric oxide synthase (nNOS; EC 1.14.13.39) mRNA species revealed NOS1 to be the most structurally diverse human gene described to date in terms of promoter usage. Nine unique exon 1 variants are variously used for transcript initiation in diverse tissues, and each is expressed from a unique 5'-flanking region. The dependence on unique genomic regions to control transcription initiation in a cell-specific fashion burdens the transcripts with complex 5'-mRNA leader sequences. Elaborate splicing patterns that involve alternatively spliced leader exons and exon skipping have been superimposed on this diversity. Highly structured nNOS mRNA 5'-untranslated regions, which have profound effects on translation both in vitro and in cells, contain cis RNA elements that modulate translational efficiency in response to changes in cellular phenotype.
authors.affiliation: Renal Division and Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON M4X 1B1, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: D C
authors.initials: DC
authors.lastname: Newton
authors.forename: G B
authors.initials: GB
authors.lastname: Robb
authors.forename: C L
authors.initials: CL
authors.lastname: Kau
authors.forename: T L
authors.initials: TL
authors.lastname: Miller
authors.forename: A H
authors.initials: AH
authors.lastname: Cheung
authors.forename: A V
authors.initials: AV
authors.lastname: Hall
authors.forename: S
authors.initials: S
authors.lastname: VanDamme
authors.forename: J N
authors.initials: JN
authors.lastname: Wilcox
authors.forename: P A
authors.initials: PA
authors.lastname: Marsden
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D017398:Alternative Splicing; D001483:Base Sequence; D005091:Exons; D014644:Genetic Variation; D006801:Humans; D017403:In Situ Hybridization; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D010641:Phenotype; D014176:Protein Biosynthesis; D012313:RNA / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D014018:Tissue Distribution
chemical_list: D020121:5' Untranslated Regions; D012313:RNA; D019001:Nitric Oxide Synthase