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

Randy Wymore, Deborah Negulescu, Keith Kinoshita, Katalin Kalman, Jayashree Aiyar, George A. Gutman, K. George Chandy

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)15629-15634
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number26
DOIs
StatePublished - 16 Jul 1996

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Voltage-Gated Potassium Channels
Transcription
Genes
Messenger RNA
Exons
Organ Specificity
Polyadenylation
Initiator Codon
Terminator Codon
Xenopus
Oocytes
Brain
Nucleotides
Tissue
Proteins

Cite this

Wymore, R., Negulescu, D., Kinoshita, K., Kalman, K., Aiyar, J., Gutman, G. A., & George Chandy, K. (1996). Characterization of the transcription unit of mouse Kv1.4, a voltage- gated potassium channel gene. Journal of Biological Chemistry, 271(26), 15629-15634. https://doi.org/10.1074/jbc.271.26.15629
Wymore, Randy ; Negulescu, Deborah ; Kinoshita, Keith ; Kalman, Katalin ; Aiyar, Jayashree ; Gutman, George A. ; George Chandy, K. / Characterization of the transcription unit of mouse Kv1.4, a voltage- gated potassium channel gene. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 26. pp. 15629-15634.
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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.",
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Wymore, R, Negulescu, D, Kinoshita, K, Kalman, K, Aiyar, J, Gutman, GA & George Chandy, K 1996, 'Characterization of the transcription unit of mouse Kv1.4, a voltage- gated potassium channel gene', Journal of Biological Chemistry, vol. 271, no. 26, pp. 15629-15634. https://doi.org/10.1074/jbc.271.26.15629

Characterization of the transcription unit of mouse Kv1.4, a voltage- gated potassium channel gene. / Wymore, Randy; Negulescu, Deborah; Kinoshita, Keith; Kalman, Katalin; Aiyar, Jayashree; Gutman, George A.; George Chandy, K.

In: Journal of Biological Chemistry, Vol. 271, No. 26, 16.07.1996, p. 15629-15634.

Research output: Contribution to journalArticle

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T1 - Characterization of the transcription unit of mouse Kv1.4, a voltage- gated potassium channel gene

AU - Wymore, Randy

AU - Negulescu, Deborah

AU - Kinoshita, Keith

AU - Kalman, Katalin

AU - Aiyar, Jayashree

AU - Gutman, George A.

AU - George Chandy, K.

PY - 1996/7/16

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N2 - 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.

AB - 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.

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