Multiple transcripts of sodium channel SCN8A (Na(V)1.6) with alternative 5'- and 3'-untranslated regions and initial characterization of the SCN8A promoter.

Department of Human Genetics, University of Michigan, 4708 Medical Science II, Ann Arbor, MI 48109-0618, USA.

To identify the transcriptional start sites of the neuronal channel SCN8A, we carried out 5'-RACE (rapid amplification of cDNA ends) with RNA from human and mouse brain. We recovered four mutually exclusive 5'-untranslated exons (exon 1a to exon 1d) that map to a 1.8-kb region of genomic DNA located approximately 70 kb upstream of the first coding exon. The same 5'-untranslated exons are expressed in central, peripheral and sympathetic nervous system and in embryonic and adult brain. A 4.8-kb genomic fragment containing these 5' exons demonstrated promoter activity in transfected MN-1 cells. In transgenic mice, transcription of the 4.8-kb promoter was restricted to brain and spinal cord. The 4.8-kb promoter contains eight consensus Sp1-binding sites and two Inr sites. A potential NRSE/RE-1 site is located nearby. Two active polyadenylation sites identified by 3'-RACE are conserved in human, mouse, and chicken SCN8A. Sequence comparison of human and mouse SCN8A identified 12 conserved noncoding elements whose effect on transcription was tested in transfected cells.

PMID: 15676283 [PubMed - indexed for MEDLINE]