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

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 () mRNA expression has been studied at both transcriptional and pre-mRNA splicing levels, the molecular mechanisms governing 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/ELAVL1) and myocyte enhancer factor-2C (MEF2C) transcription factor mRNA are associated. HuR positively regulated transcription factor MEF2C 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, MEF2C enhanced transcription by binding to a putative MEF2C binding site within promoter region. Overexpression of HuR increased the expression of mRNA, and this effect was attenuated by the presence of MEF2C 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 mRNA expression. HuR upregulates MEF2C mRNA expression by protecting MEF2C mRNA from degradation, and consequently, the elevated MEF2C enhances mRNA transcription.