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• W2303220740 abstract "Abstract Alternative pre‐mRNA splicing is a fundamental regulatory process for most mammalian multi‐exon genes to increase proteome diversity. Nonsense‐mediated mRNA decay (NMD) is a conserved mRNA surveillance mechanism to mitigate deleterious effects caused by gene mutations or transcriptional errors. Coupling alternative splicing and NMD (AS‐NMD), in which alternative splicing switches between translational and NMD isoforms, results in fine‐tuning overall gene expression to, in turn, expand the functional activities of these two post‐transcriptional regulatory processes. AS‐NMD is known for maintaining homeostatic expression of many RNA‐binding proteins. We further show that AS‐NMD is a conserved mechanism among mammals to induce developmental expression of the synaptic scaffold protein PSD‐95. Comparing gene sequences between human Psd‐95 and its ancestral orthologues indicates that AS‐NMD regulation of mammalian Psd‐95 is a product of selective pressure and that it enforces neural‐specific expression of PSD‐95 proteins in mammals. Invertebrate homolog of Psd‐95 is not subjected to AS‐NMD regulation and its protein product does not exhibit neural‐specific expression. Given the prevalence of alternative splicing regulation in the mammalian nervous system, neural‐specific expression of many other genes could be controlled by AS‐NMD in a similar manner. We discuss the implication of these discoveries, as well as the challenges in generalizing the regulation and functional activity of AS‐NMD." @default.
• W2303220740 created "2016-06-24" @default.
• W2303220740 creator A5028346806 @default.
• W2303220740 date "2016-03-08" @default.
• W2303220740 modified "2023-09-30" @default.
• W2303220740 title "Alternative splicing and nonsense‐mediated mRNA decay enforce neural specific gene expression" @default.
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• W2303220740 doi "https://doi.org/10.1016/j.ijdevneu.2016.03.003" @default.
• W2303220740 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5016260" @default.
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