Expression regulation of SCN1A
SCN1A gene has a complex 5′-untranslated region (5′UTR) with 6 to 8 alternatively spliced noncoding exons and several different transcription start sites (TSS). The 5′UTR spans about 75 kb of genomic sequence. Three SCN1A promoters have been identified to be located on the upstream of three 5′-noncoding exons (1a, 1b, and 1c). The 5′UTR plays an important role in SCN1A expression, which is also regulated by other transcriptional factors. For instance, we recent identified a silencer downstream of the SCN1A P1c promoter, to which a scaffolding protein RACK1 binds and subsequently represses SCN1A transcription in human NT2 cells. Deprivation of the binding of RACK1 to the silencer may upregulate SCN1A transcription, as shown in neuron-like differentiated NT2 cells (DOI 10.1007/s12035-014-8633-9).
The 3′-untranslated region (3′UTR) of SCN1A gene may play a critical but still less unveiled role in regulating gene expression at the posttranscriptional level. As shown in one of our recent studies, a mutation at SCN1A 3′UTR may create novel binding site of GAPDH to cis-element and decrease mRNA stability, and being potentially associated with SCN1A-related diseases (DOI 10.1007/s00439-014-1422-8).
Copyright ©2014 Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China
Collaborative Innovation Center for Neurogenetics and Channelopathies, Guangzhou 510260, China.