The genomic basis of K(V)3.4 potassium channel mRNA diversity in mice.
Gene
; 264(1): 29-35, 2001 Feb 07.
Article
em En
| MEDLINE
| ID: mdl-11245975
ABSTRACT
K(V)3.4 belongs to the shaw subfamily of shaker-type potassium channels. It conducts fast inactivating, high threshold currents in the central nervous system and in fast-twitch skeletal muscle fibers. The corresponding mouse gene, Kcnc4, consists of five exons spanning a region of 20 kb. Approximately 700 bp of regulatory sequence were delineated. It is GC-rich and lacks typical TATA and CAAT motifs. Instead, seven Sp-1 and three E-box elements define putative regulatory sequences. The mouse K(V)3.4 mRNA has a size of 3639 bp, 1120 bp of which are 3' untranslated region. A transcript initiated from an alternative 5'-exon was identified by RACE and verified by genomic analysis. This isoform, designated K(V)3.4d, is predominantly expressed in skeletal muscle and probably results from alternative promoter usage. It encodes a channel protein with a novel N-terminal cytoplasmic domain. It lacks the conserved sequence motifs encoding the shaw-type tetramerization domain and the 'ball' peptide, which confers fast inactivation properties. Another splice variant, K(V)3.4c, is derived by exon skipping in the C-terminal region and is expressed at similar levels in brain and muscle. These data demonstrate that differential splicing and alternative transcription start sites are utilised to generate a set of K(V)3.4 variants in skeletal muscle and brain, presumably involved in the regulation of excitability.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Canais de Potássio
/
Canais de Potássio de Abertura Dependente da Tensão da Membrana
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Genes
Limite:
Animals
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article