RNA diversity has profound effects on the translation of neuronal nitric oxide synthase.
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.
Wang
Y
Y
Renal Division and Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON M4X 1B1, Canada.
Newton
D C
DC
Robb
G B
GB
Kau
C L
CL
Miller
T L
TL
Cheung
A H
AH
Hall
A V
AV
VanDamme
S
S
Wilcox
J N
JN
Marsden
P A
PA
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
D020121:5' Untranslated Regions; D012313:RNA; D019001:Nitric Oxide Synthase