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

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

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  • 1Renal Division and Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON M4X 1B1, Canada.


A comprehensive analysis of the structure of neuronal nitric oxide synthase (nNOS; EC 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.

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