A study published in the journal Function highlights the importance of not studying exon splicing in isolation. Exon splicing is the process by which introns are removed from the pre-mRNA and exons are re-spliced together.
The researchers were initially studying the functional importance of the short versus long version of exon 47 present in a specific calcium channel called the N-type channel that is important for the release of neurotransmitters. Release of the N-type channel at the first synapse in the spinal cord pain pathway makes it a target for drug discovery.
In available sequence databases, short exon 47 was only present in channel sequences containing no other exons, according to researchers at University College London. Additionally, the researchers found that long exon 47 resulted in significantly greater N-type calcium channel currents than the other three combinations only if exon 18a was present.
In comparison, cell surface channel expression was increased by long exon 47 as opposed to short exon 47, whether exon 18a was present or not. Thus, the additional presence of exon 18a must affect channel function by increasing its ability to open, rather than by increasing the amount of channel on the cell surface.
“Our study highlights the importance of investigating the combinatorial effects of including exons, rather than each in isolation, to increase our understanding of how calcium channels function and for future drug discovery,” said Annette Dolphin , Ph.D., one of the authors. of the study.
Shehrazade Dahimene et al, Interaction between splicing of two exon combinations differentially affects membrane targeting and function of human CaV2.2, Function (2023). DOI: 10.1093/function/zqad060
Provided by the American Physiological Society
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