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Chk2-dependent HuR phosphorylation regulates occludin mRNA translation and epithelial barrier function
Ting-Xi Yu1, Peng-Yuan Wang, Jaladanki N Rao
1Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore Street, Baltimore, MD 21201, USA.
Nucleic Acids Research
|July 13, 2011
Summary
The RNA-binding protein HuR enhances occludin translation via Chk2-dependent phosphorylation, crucial for intestinal epithelial barrier function. Septic stress impairs this pathway, leading to gut barrier dysfunction.
Area of Science:
- Molecular Biology
- Cell Biology
- Gastroenterology
Background:
- Occludin is a key transmembrane protein regulating epithelial barrier function.
- Post-transcriptional regulation of occludin remains largely unelucidated.
- HuR (human antigen R) is an RNA-binding protein known to affect mRNA stability and translation.
Purpose of the Study:
- To investigate the role of HuR in occludin expression.
- To elucidate the mechanisms of HuR-mediated occludin regulation.
- To determine the impact on intestinal epithelial barrier function.
Main Methods:
- Investigated HuR binding to the 3'-untranslated region of occludin mRNA.
- Utilized Chk2 silencing and overexpression to assess its effect on HuR phosphorylation and occludin translation.
- Examined occludin expression and gut barrier function in a mouse model of septic stress.
Main Results:
- HuR directly binds to occludin mRNA, enhancing its translation.
- HuR's association with occludin mRNA is dependent on Chk2-mediated HuR phosphorylation.
- Reduced Chk2 activity or levels decrease HuR-occludin mRNA binding and occludin translation.
- Septic stress in mice leads to decreased Chk2, reduced occludin expression, and impaired gut barrier function.
Conclusions:
- HuR regulates occludin mRNA translation through Chk2-dependent phosphorylation.
- This regulatory pathway is vital for maintaining intestinal epithelial barrier integrity.
- Dysregulation of this mechanism contributes to gut barrier dysfunction during septic stress.
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