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Background <p>The degree to which alternative RNA splicing influences the function and structure of voltage gated calcium channel (VGCC) splice variants is poorly understood. Here we used long-read RNA-sequencing to catalog rat <i>Cacna1e</i> (Cav2.3) splice variants, and computationally prioritize which are likely to impact channel function.</p> Result <p>We sequenced <i>Cacna1e</i> transcripts from rat thalamus using Oxford Nanopore sequencing yielding the structure of 2,110 <i>Cacna1e</i> splice variants. Of these, up to 154 had the potential encode for a functional channel based on predicted amino acid sequences. Our analysis revealed a total of 31 cassette splicing events (in various combinations) potentially affecting channel function, with three cassette exons appreciably expressed and conserved.</p> Conclusion <p>Our work both provides the first long-read sequencing of <i>Cacna1e</i> and the first computational evaluation of <i>Cacna1e</i> splice variants for future follow-up. This overall strategy to provide the field with prioritized transcripts will improve our understanding of <i>Cacna1e</i> function, its role in disease pathophysiology, and serve as a general approach to evaluate splice variant function across multiple ion channel types.</p>

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Cataloging the potential functional diversity of Cacna1e splice variants using long-read sequencing

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月26日

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  • Shamsuddin A. Bhuiyan,
  • John R. Tyson,
  • Manuel Belmadani,
  • Jordan Sicherman,
  • Terrance P. Snutch,
  • Paul Pavlidis

摘要

Background

The degree to which alternative RNA splicing influences the function and structure of voltage gated calcium channel (VGCC) splice variants is poorly understood. Here we used long-read RNA-sequencing to catalog rat Cacna1e (Cav2.3) splice variants, and computationally prioritize which are likely to impact channel function.

Result

We sequenced Cacna1e transcripts from rat thalamus using Oxford Nanopore sequencing yielding the structure of 2,110 Cacna1e splice variants. Of these, up to 154 had the potential encode for a functional channel based on predicted amino acid sequences. Our analysis revealed a total of 31 cassette splicing events (in various combinations) potentially affecting channel function, with three cassette exons appreciably expressed and conserved.

Conclusion

Our work both provides the first long-read sequencing of Cacna1e and the first computational evaluation of Cacna1e splice variants for future follow-up. This overall strategy to provide the field with prioritized transcripts will improve our understanding of Cacna1e function, its role in disease pathophysiology, and serve as a general approach to evaluate splice variant function across multiple ion channel types.