RBM25LUC7L3 review 8 2 2012.pdf (409.34 kB)
Download file

RBM25/LUC7L3 function in Cardiac Sodium Channel Splicing Regulation of Human Heart Failure

Download (409.34 kB)
journal contribution
posted on 19.11.2013, 00:00 authored by Ge Gao, Samuel C. Jr. Dudley
Alternative splicing is a post-transcriptional mechanism that can substantially change the pattern of gene expression. Up to 95% of human genes have multi-exon alternative spliced forms, suggesting that alternative splicing is one of the most significant components of the functional complexity of the human genome. Nevertheless, alternative splicing regulation has received comparatively little attention in the study of cardiac diseases. When investigating SCN5A splicing abnormalities in heart failure, we found 47 of 181 known splicing regulators were upregulated in HF when compared to controls, which indicate that splicing regulation may play a key role in heart failure. Our results shows that AngII and hypoxia, signals common to HF, result in increased LUC7L3 and RBM25 splicing regulators, increased binding of RBM25 to SCN5A mRNA, increased SCN5A splice variant abundances, decreased full-length SCN5A mRNA and protein, and decreased Na+ current. These observations could shed light on a mechanism whereby cardiac function and arrhythmic risk are associated and allow for refined predictions of which patients may be at highest arrhythmic risk or suffer from Na+ channel blocking anti-arrhythmic drug complications.

Funding

This work was supported by R01 HL106592, R01 HL104025, P01 HL058000 (SCD), and a VA MERIT grant.

History

Publisher Statement

NOTICE: This is the author’s version of a work that was accepted for publication in Trends in Cardiovascular Medicine. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Trends in Cardiovascular Medicine, (2012) DOI: 10.1016/j.tcm.2012.08.003

Publisher

Elsevier

Language

en_US

issn

1873-2615

Issue date

01/08/2012

Usage metrics

Categories

Keywords

Exports