Alternative Processing: Neuronal Nitric Oxide Synthase

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Abstract The human neuronal nitric oxide synthase (nNOS) gene is expressed from multiple promoters and is subject to alternate messenger ribonucleic acid (mRNA) processing. These complex molecular mechanisms contribute to regulating gene expression and function in multiple tissues and cell types. In the case of nNOS, these distinct promoters give rise to mRNA transcripts with untranslated leader sequences that have differing lengths, nucleotide composition and three‐dimensional structure. These distinct leader sequences have robust effects on translational efficiency. In disease settings, these have functional relevance. For example, in settings of low oxygen content, a unique promoter becomes transcriptionally active. In contrast to basally expressed transcripts, this hypoxia‐induced mRNA is very efficiently translated. To accommodate diverse biological roles, multiple mechanisms have evolved to produce a diverse range of nNOS mRNA transcripts from a single genetic locus. Key Concepts Mammalian genes can have more than one promoter. Having more than one promoter implies that the gene has more than one version of exon 1. Initiation of transcription in different regions of genomic DNA imparts different nucleotide sequences to the leader regions of messenger ribonucleic acid transcripts, also known as the 5′‐untranslated region (5′‐UTR). Different leader sequences may, or may not, affect protein structure depending on whether the initiator AUG codon for translation of the protein lies in exon 1 or downstream. If multiple versions of exon 1 all have their own initiator AUG codon, then the encoded protein will exist in different forms, each with a unique N ‐terminal peptide sequence. Different 5′‐UTRs of messenger ribonucleic acid transcripts can have functional effects on expression of the encoded protein. The 5′‐UTRs of messenger ribonucleic acid transcripts can affect translational efficiency. The 5′‐UTRs of messenger ribonucleic acid transcripts can affect subcellular messenger ribonucleic acid transcript localisation. The 5′‐UTRs of messenger ribonucleic acid transcripts can affect messenger ribonucleic acid transcript stability. Factors that regulate chromatin and transcription complexes can impact the splicing process.