RNA binding protein, HuR, regulates SCN5A expression through stabilizing MEF2C transcription factor mRNA

Anyu Zhou, Guangbin Shi, Gyeoung Jin Kang, An Xie, Hong Liu, Ning Jiang, Man Liu, Euy Myoung Jeong, Samuel C. Dudley

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 a-subunit (SCN5A) mRNA expression has been studied at both transcriptional and pre-mRNA splicing levels, the molecular mechanisms governing SCN5A 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 SCN5A transcription by binding to a putative MEF2C binding site within SCN5A promoter region. Overexpression of HuR increased the expression of SCN5A 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 SCN5A mRNA expression. HuR upregulates MEF2C mRNA expression by protecting MEF2C mRNA from degradation, and consequently, the elevated MEF2C enhances SCN5A mRNA transcription.

Original languageEnglish (US)
Article numbere007802
JournalJournal of the American Heart Association
Volume7
Issue number9
DOIs
StatePublished - May 1 2018

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MEF2 Transcription Factors
RNA-Binding Proteins
Transcription Factors
Messenger RNA
RNA Stability
ELAV Proteins
Gene Expression
Ribonucleoproteins
Sodium Channels
Chromatin Immunoprecipitation
RNA Precursors
Gene Expression Regulation
Electrophoretic Mobility Shift Assay
Immunoprecipitation
Cardiac Myocytes
Genetic Promoter Regions
Small Interfering RNA
Up-Regulation
Binding Sites
RNA

Keywords

  • Mef2c
  • Sodium channel α-subunit
  • Transcription factors
  • Transcriptional regulation

Cite this

RNA binding protein, HuR, regulates SCN5A expression through stabilizing MEF2C transcription factor mRNA. / Zhou, Anyu; Shi, Guangbin; Kang, Gyeoung Jin; Xie, An; Liu, Hong; Jiang, Ning; Liu, Man; Jeong, Euy Myoung; Dudley, Samuel C.

In: Journal of the American Heart Association, Vol. 7, No. 9, e007802, 01.05.2018.

Research output: Contribution to journalArticle

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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 a-subunit (SCN5A) mRNA expression has been studied at both transcriptional and pre-mRNA splicing levels, the molecular mechanisms governing SCN5A 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 SCN5A transcription by binding to a putative MEF2C binding site within SCN5A promoter region. Overexpression of HuR increased the expression of SCN5A 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 SCN5A mRNA expression. HuR upregulates MEF2C mRNA expression by protecting MEF2C mRNA from degradation, and consequently, the elevated MEF2C enhances SCN5A mRNA transcription.",
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T1 - RNA binding protein, HuR, regulates SCN5A expression through stabilizing MEF2C transcription factor mRNA

AU - Zhou, Anyu

AU - Shi, Guangbin

AU - Kang, Gyeoung Jin

AU - Xie, An

AU - Liu, Hong

AU - Jiang, Ning

AU - Liu, Man

AU - Jeong, Euy Myoung

AU - Dudley, Samuel C.

PY - 2018/5/1

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N2 - 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 a-subunit (SCN5A) mRNA expression has been studied at both transcriptional and pre-mRNA splicing levels, the molecular mechanisms governing SCN5A 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 SCN5A transcription by binding to a putative MEF2C binding site within SCN5A promoter region. Overexpression of HuR increased the expression of SCN5A 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 SCN5A mRNA expression. HuR upregulates MEF2C mRNA expression by protecting MEF2C mRNA from degradation, and consequently, the elevated MEF2C enhances SCN5A mRNA transcription.

AB - 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 a-subunit (SCN5A) mRNA expression has been studied at both transcriptional and pre-mRNA splicing levels, the molecular mechanisms governing SCN5A 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 SCN5A transcription by binding to a putative MEF2C binding site within SCN5A promoter region. Overexpression of HuR increased the expression of SCN5A 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 SCN5A mRNA expression. HuR upregulates MEF2C mRNA expression by protecting MEF2C mRNA from degradation, and consequently, the elevated MEF2C enhances SCN5A mRNA transcription.

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