RNA Binding Protein, HuR, Regulates SCN5A Expression Through Stabilizing MEF2C transcription factor mRNA

Abstract

Background Although transcription is the initial process of gene expression, posttranscriptional gene expression regulation has also played a critical role for fine‐tuning gene expression in a fast, precise, and cost‐effective manner. Although the regulation of sodium channel α‐subunit ( SCN 5A ) mRNA expression has been studied at both transcriptional and pre‐ mRNA splicing levels, the molecular mechanisms governing SCN 5A mRNA expression are far from clear. Methods and Results Herein, we show that, as evidenced by ribonucleoprotein immunoprecipitation assay, RNA binding protein Hu antigen R/ELAV like RNA binding protein 1 (HuR/ ELAVL 1) and myocyte enhancer factor‐2C (MEF2C) transcription factor mRNA are associated. HuR positively regulated transcription factor MEF 2C mRNA expression by protecting its mRNA from degradation. As demonstrated by both chromatin immunoprecipitation–quantitative polymerase chain reaction assay and an electrophoretic mobility shift assay, MEF 2C enhanced SCN 5A transcription by binding to a putative MEF 2C binding site within SCN 5A promoter region. Overexpression of HuR increased the expression of SCN 5A mRNA , and this effect was attenuated by the presence of MEF 2C small interfering RNA in cardiomyocytes. Conclusions In conclusion, our results suggested that HuR participates in a combined network at the DNA and RNA levels that regulates SCN 5A mRNA expression. HuR upregulates MEF 2C mRNA expression by protecting MEF 2C mRNA from degradation, and consequently, the elevated MEF 2C enhances SCN 5A mRNA transcription.