Alternative promoter usage and splicing of the human SCN5A gene contribute to transcript heterogeneity

Leonie Van Stuijvenberg, Cansu Yildirim, Bart G J M Kok, Toon A B Van Veen, A. Varró, Stephan K G Winckels, Marc A. Vos, Marti F A Bierhuizen

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The sodium channel isoform Nav1.5 mediates sodium current, excitability, and electrical conduction in the human heart. Recent studies have indicated alternative splicing within the protein-coding portion of its gene, SCN5A, as a mechanism to generate diversity in Nav1.5 protein structure and function. In the present study we identified several novel SCN5A transcripts in human heart, displaying distinct 5'-untranslated regions but identical protein-coding sequences. These transcripts originated from the splicing of alternative exons 1 (designated 1A, 1B, 1C, and 1D) to the translational start codon-containing exon 2, and were preferentially expressed in the heart as compared to other tissues. Comparison of their expression level between adult and fetal heart demonstrated that exon 1C- and 1D-derived sequences were more prominent in adult than in fetal heart. Two new promoters (designated P2 and P3) for the SCN5A gene were identified and functionally characterized in myocardial- and nonmyocardial-derived cell lines. Translation of the transcript containing exon 1D-derived sequences proved to be significantly impaired in these cell lines, which could be restored by mutation of an upstream translational start codon. These results implicate the usage of alternative promoters and 5'-untranslated regions as new mechanisms in the regulation of human Nav1.5 expression.

Original languageEnglish
Pages (from-to)577-587
Number of pages11
JournalDNA and Cell Biology
Volume29
Issue number10
DOIs
Publication statusPublished - Oct 1 2010

Fingerprint

Exons
Fetal Heart
Initiator Codon
5' Untranslated Regions
Alternative Splicing
Genes
Cell Line
Proteins
Sodium Channels
Protein Isoforms
Sodium
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology
  • Medicine(all)

Cite this

Van Stuijvenberg, L., Yildirim, C., Kok, B. G. J. M., Van Veen, T. A. B., Varró, A., Winckels, S. K. G., ... Bierhuizen, M. F. A. (2010). Alternative promoter usage and splicing of the human SCN5A gene contribute to transcript heterogeneity. DNA and Cell Biology, 29(10), 577-587. https://doi.org/10.1089/dna.2009.0999

Alternative promoter usage and splicing of the human SCN5A gene contribute to transcript heterogeneity. / Van Stuijvenberg, Leonie; Yildirim, Cansu; Kok, Bart G J M; Van Veen, Toon A B; Varró, A.; Winckels, Stephan K G; Vos, Marc A.; Bierhuizen, Marti F A.

In: DNA and Cell Biology, Vol. 29, No. 10, 01.10.2010, p. 577-587.

Research output: Contribution to journalArticle

Van Stuijvenberg, L, Yildirim, C, Kok, BGJM, Van Veen, TAB, Varró, A, Winckels, SKG, Vos, MA & Bierhuizen, MFA 2010, 'Alternative promoter usage and splicing of the human SCN5A gene contribute to transcript heterogeneity', DNA and Cell Biology, vol. 29, no. 10, pp. 577-587. https://doi.org/10.1089/dna.2009.0999
Van Stuijvenberg, Leonie ; Yildirim, Cansu ; Kok, Bart G J M ; Van Veen, Toon A B ; Varró, A. ; Winckels, Stephan K G ; Vos, Marc A. ; Bierhuizen, Marti F A. / Alternative promoter usage and splicing of the human SCN5A gene contribute to transcript heterogeneity. In: DNA and Cell Biology. 2010 ; Vol. 29, No. 10. pp. 577-587.
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