Back to Search Start Over

Inhibition of minor intron splicing reduces Na+ and Ca2+ channel expression and function in cardiomyocytes.

Authors :
Montañés-Agudo, Pablo
Casini, Simona
Aufiero, Simona
Ernault, Auriane C.
van der Made, Ingeborg
Pinto, Yigal M.
Remme, Carol Ann
Creemers, Esther E.
Source :
Journal of Cell Science. 12/15/2022, Vol. 135 Issue 24, p1-11. 11p.
Publication Year :
2022

Abstract

Eukaryotic genomes contain a tiny subset of 'minor class' introns with unique sequence elements that require their own splicing machinery. These minor introns are present in certain gene families with specific functions, such as voltage-gated Na+ and voltage-gated Ca2+ channels. Removal of minor introns by the minor spliceosome has been proposed as a post-transcriptional regulatory layer, which remains unexplored in the heart. Here, we investigate whether the minor spliceosome regulates electrophysiological properties of cardiomyocytes by knocking down the essential minor spliceosome small nuclear snRNA component U6atac in neonatal rat ventricular myocytes. Loss of U6atac led to robust minor intron retention within Scn5a and Cacna1c, resulting in reduced protein levels of Nav1.5 and Cav1.2 channels. Functional consequences were studied through patch-clamp analysis, and revealed reduced Na+ and L-type Ca2+ currents after loss of U6atac. In conclusion, minor intron splicing modulates voltage-dependent ion channel expression and function in cardiomyocytes. This may be of particular relevance in situations in which minor splicing activity changes, such as in genetic diseases affecting minor spliceosome components, or in acquired diseases in which minor spliceosome components are dysregulated, such as heart failure. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00219533
Volume :
135
Issue :
24
Database :
Academic Search Index
Journal :
Journal of Cell Science
Publication Type :
Academic Journal
Accession number :
161273857
Full Text :
https://doi.org/10.1242/jcs.259191