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(Received for publication, November 30, 1995, and in revised form, February 7, 1996)
From the Departments of Physiology and Biophysics and
¶ Microbiology and Molecular Genetics, University of
California, Irvine, California 92717 and the 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
Volume 271, Number 26,
Issue of June 28, 1996
pp. 15629-15634
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
Department
of Physiology and Biophysics, State University of New York, Stony
Brook, New York 11794
-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.
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