Characterization of the transcription unit of mouse Kv1.4, a voltage- gated potassium channel gene

Abstract

The mouse voltage-gated K + channel gene, Kv1.4, is expressed in brain and heart as ~4.5- and ~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 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.