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 similar to 4.5- and similar to 3.5-kilobase kb) transcrip ts. Both mRNAs begin at a common site 1338 bp upstream of the initiati on codon, contain 3477 and 4411 nucleotides, respectively, and are enc oded 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 ent ire 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, w hile the 4.5-kb mRNA utilizes a signal 94 bp farther downstream. Altho ugh the proteins generated hom either transcript are identical, the tw o mRNAs are functionally different, the 3.5-kb transcript producing si milar to 4-5-fold larger currents when expressed in Xenopus oocytes co mpared to the 4.5-kb mRNA. The decreased expression of the longer tran script is due to the presence of five ATTTA repeats in the 3'-NCR whic h inhibit translation; such motifs have also been reported to destabil ize the messages of many other genes and might therefore shorten the l ife 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. Thu s, transcriptional and post-transcriptional regulation of mKv1.4, coup led with selective usage of the two alternate Kv1.4 mRNAs, may modulat e the levels of functional Kv1.4 channels.