2012
DOI: 10.1016/j.mcn.2011.10.005
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Rbfox proteins regulate alternative splicing of neuronal sodium channel SCN8A

Abstract: The SCN8A gene encodes the voltage-gated sodium channel Nav1.6, a major channel in neurons of the CNS and PNS. SCN8A contains two alternative exons, 18N and 18A, that exhibit tissue specific splicing. In brain, the major SCN8A transcript contains exon 18A and encodes the full-length sodium channel. In other tissues, the major transcript contains exon 18N and encodes a truncated protein, due to the presence of an in-frame stop codon. Selection of exon 18A is therefore essential for generation of a functional ch… Show more

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Cited by 44 publications
(47 citation statements)
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“…Moreover, exon 18A has been shown to be activated by ectopically expressed Fox proteins. This enhancement is dependent on the first downstream UGCAUG element, which is conserved in vertebrates (O'Brien et al 2011). As predicted, exon 5A splicing is moderately decreased in Rbfox2 À/À and Rbfox1 À/À whole-brain RNA (Table 1; Gehman et al 2011) and in the cerebellum (Fig.…”
Section: Rbfox2-dependent Splicing In Cerebellum Genes and Development 453supporting
confidence: 74%
See 1 more Smart Citation
“…Moreover, exon 18A has been shown to be activated by ectopically expressed Fox proteins. This enhancement is dependent on the first downstream UGCAUG element, which is conserved in vertebrates (O'Brien et al 2011). As predicted, exon 5A splicing is moderately decreased in Rbfox2 À/À and Rbfox1 À/À whole-brain RNA (Table 1; Gehman et al 2011) and in the cerebellum (Fig.…”
Section: Rbfox2-dependent Splicing In Cerebellum Genes and Development 453supporting
confidence: 74%
“…In domain III, exon 18A encodes the full S3-to-S4 segment. However, Exon 18N contains a conserved in-frame stop codon that prematurely truncates the reading frame, leading to nonsensemediated mRNA decay (Plummer et al 1997;O'Brien et al 2011). Still another mRNA isoform, the D18 transcript, maintains the original reading frame, but lacks segments S3 and S4 of domain III altogether.…”
Section: Rbfox2-dependent Splicing In Cerebellum Genes and Development 453mentioning
confidence: 99%
“…Another pair of mutually exclusive exons, 18A and 18N, determine whether a functional 18A+ Scn8a mRNA is produced. Inclusion of 18N introduces a premature termination codon and leads to nonsense-mediated decay, whereas skipping both 18A and 18N produces an isoform that lacks large portions of the third and fourth transmembrane domains 146,147 (FIG. 4b).…”
Section: Regulation Of Synaptic Functionmentioning
confidence: 99%
“…Adult levels of expression and splicing are reached by 1 month in the mouse, 37,38 and between 1 and 9 years of age in humans. 39 Expression of Na v 1.6 is widespread throughout the central and peripheral nervous system in both excitatory and inhibitory neurons. 29,37 An important aspect of Na v 1.6 biology is its concentration at two specialized membrane domains: the axon initial segment (the site of action potential initiation) and the node of Ranvier (the site of action potential regeneration during axonal saltatory conduction).…”
Section: Characteristics Of Sodium Channel Nav16 Encoded By Scn8amentioning
confidence: 99%