Characterization of the transcription unit of mouse Kv1.4, a voltage-gated potassium channel gene.
The mouse voltage-gated K+ channel gene, Kv1.4, is expressed in brain and heart as approximately 4.5- and approximately 3.5-kilobase (kb) transcripts. Both mRNAs begin at a common site 1338 bp upstream of the initiation codon, contain 3477 and 4411 nucleotides, respectively, and are encoded by two exons; exon 1 contains 0.5 kb of the 5'-noncoding region (NCR), while exon 2 encodes the remaining 0.8 kb of the 5'-NCR, the entire coding region (2 kb), and all of the 3'-NCR. The 3.5-kb transcript terminates at a polyadenylation signal 177 bp 3' of the stop codon, while the 4.5-kb mRNA utilizes a signal 94 bp farther downstream. Although the proteins generated from either transcript are identical, the two mRNAs are functionally different, the 3.5-kb transcript producing approximately 4-5-fold larger currents when expressed in Xenopus oocytes compared to the 4. 5-kb mRNA. The decreased expression of the longer transcript is due to the presence of five ATTTA repeats in the 3'-NCR which inhibit translation; such motifs have also been reported to destabilize the messages of many other genes and might therefore shorten the life of the 4.5-kb transcript during its natural expression. The Kv1.4 basal promoter is GC-rich, contains three SP1 repeats (CCGCCC, -65 to -35), lacks canonical TATAAA and GGCAATCT motifs, and has no apparent tissue specificity. One region enhances activity of this promoter. Thus, transcriptional and post-transcriptional regulation of mKv1.4, coupled with selective usage of the two alternate Kv1.4 mRNAs, may modulate the levels of functional Kv1.4 channels.
Wymore
R S
RS
Department of Physiology, University of California, Irvine, California 92717, USA.
Negulescu
D
D
Kinoshita
K
K
Kalman
K
K
Aiyar
J
J
Gutman
G A
GA
Chandy
K G
KG
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005796:Genes; D008564:Membrane Potentials; D051379:Mice; D009865:Oocytes; D015221:Potassium Channels / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014982:Xenopus laevis
D015221:Potassium Channels; D012333:RNA, Messenger