title: Characterization of 5' untranslated regions of the voltage-gated sodium channels SCN1A, SCN2A, and SCN3A and identification of cis-conserved noncoding sequences.
abstract: The human voltage-gated sodium channel gene cluster on chromosome 2q24 contains three paralogs, SCN1A, SCN2A, and SCN3A, which are expressed in the central nervous system. Mutations in SCN1A and SCN2A cause several subtypes of idiopathic epilepsy. Furthermore, many SCN1A mutations are predicted to reduce protein levels, emphasizing the importance of precise sodium channel gene regulation. To investigate the genetic factors that regulate the expression of SCN1A, SCN2A, and SCN3A, we characterized the 5' untranslated region of each gene. We identified multiple noncoding exons and observed brain region differences in the expression levels of noncoding exons. Comparative sequence analysis revealed 33 conserved noncoding sequences (CNSs) between the orthologous mammalian genes and 6 CNSs between the three human paralogs. Seven CNSs corresponded to noncoding exons. Twelve CNSs were evaluated for their ability to alter the transcription of a luciferase reporter gene, and 3 resulted in a modest, but statistically significant change.
authors.affiliation: Department of Human Genetics, Emory University, Atlanta, GA 30322, USA.
authors.forename: Melinda S
authors.initials: MS
authors.lastname: Martin
authors.forename: Bin
authors.initials: B
authors.lastname: Tang
authors.forename: Nga
authors.initials: N
authors.lastname: Ta
authors.forename: Andrew
authors.initials: A
authors.lastname: Escayg
mesh_terms: D020121:5' Untranslated Regions / Q000737:chemistry*; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017124:Conserved Sequence; D005091:Exons; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062552:NAV1.3 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics*; D014162:Transfection
chemical_list: D020121:5' Untranslated Regions; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062552:NAV1.3 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C568242:SCN1A protein, human; C568251:SCN2A protein, human; C424715:SCN3A protein, human; C568249:Scn1a protein, mouse; C000654500:Scn2a protein, mouse; D015222:Sodium Channels