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 structural ly diverse human gene described to date in terms of promoter usage. Nine un ique exon 1 variants are variously used for transcript initiation in divers e tissues, and each is expressed from a unique 5'-flanking region. The depe ndence on unique genomic regions to control transcription initiation in a c ell-specific fashion burdens the transcripts with complex 5'-mRNA leader se quences. Elaborate splicing patterns that involve alternatively spliced lea der exons and exon skipping have been superimposed on this diversity. Highl y structured nNOS mRNA 5'-untranslated regions, which have profound effects on translation both in vitro and in cells, contain cis RNA elements that m odulate translational efficiency in response to changes in cellular phenoty pe.