Post-transcriptional Regulation of C-reactive Protein by the RNA-binding Protein HuR

Monday, September 22, 2014 — Poster Session II
4:00 p.m. – 6:00 p.m.	FAES Academic Center	NIA	MOLBIO-8

* FARE Award Winner

Authors

• Y Kim
• N Noren Hooten
• MK Evans

Abstract

C-reactive protein (CRP), an acute phase reactant, has been widely used as a validated clinical biomarker of the inflammatory state and an independent predictor of cardiovascular disease (CVD). Accordingly, high levels of CRP are currently used to assess cardiovascular disease risk and treatment. However, despite the critical role of CRP in CVD, the mechanisms that regulate CRP expression are not well understood. Given the AU-rich regions in the CRP 3’-untranslated region (UTR), we hypothesized that CRP may be regulated post-transcriptionally by the RNA-binding protein (RBP) HuR. We found that HuR binds directly to CRP mRNA and interacts with several regions of CRP mRNA within the 3’UTR. Through these interactions, HuR selectively increased CRP mRNA stability, since silencing HuR lowered CRP mRNA half-life and decreased CRP mRNA and protein levels compared with control siRNA transfection. Conversely, HuR overexpression increased the level of CRP mRNA. Furthermore, treatment with the age-associated inflammatory cytokine IL-6 increased binding of HuR to CRP mRNA. In summary, HuR controls CRP expression by influencing CRP mRNA stability. Post-transcriptional regulation of CRP by HuR has the potential to lead to the development of treatments for inflammatory processes that cause cardiovascular disease and age-related diseases.

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