RNA diversity has profound effects on the translation of neuronal nitric oxide synthase

Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):12150-5. doi: 10.1073/pnas.96.21.12150.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5' Untranslated Regions / genetics
  • Alternative Splicing
  • Base Sequence
  • Exons
  • Genetic Variation
  • Humans
  • In Situ Hybridization
  • Models, Genetic
  • Molecular Sequence Data
  • Neurons / enzymology*
  • Nitric Oxide Synthase / genetics*
  • Phenotype
  • Protein Biosynthesis
  • RNA / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Deletion
  • Tissue Distribution

Substances

  • 5' Untranslated Regions
  • RNA
  • Nitric Oxide Synthase

Associated data

  • GENBANK/AF049712
  • GENBANK/AF049713
  • GENBANK/AF049714
  • GENBANK/AF049715
  • GENBANK/AF049716
  • GENBANK/AF049717
  • GENBANK/AF049718
  • GENBANK/AF049719
  • GENBANK/AF049720