Chenodeoxycholic acid stabilization of LDL receptor mRNA depends on 3′-untranslated region and AU-rich element-binding protein

Human low-density lipoprotein receptor (LDLR) mRNA is unstable and contains four AU-rich elements (AREs) in the 3′-untranslated region (3′-UTR). The aim of this study was to verify the involvement of the 3′-UTR in the rapid degradation of LDLR mRNA. This study revealed that the 3′-UTR is necessary and sufficient for the degradation, and that the 1st ARE (ARE1) close to the stop codon associates with cytoplasmic proteins, and is primarily responsible for the degradation. Chenodeoxycholic acid (CDCA) treatment stabilized chimeric GFP-LDLR 3′-UTR mRNA and accompanied mitogen-activated protein kinase (MAPK) activation. The UV cross-linking assays showed that a protein of 80 kDa increasingly binds to the region including the ARE1 in response to CDCA-mediated MAPK activation.

► Chimeric GFP-LDLR 3′-UTR (2.5 kb) mRNA was rapidly degraded. ► The 600-base region of the 3′-UTR is vital for a rapid turnover and the mRNA stabilization by chenodeoxycholic acid. ► The 1st AU-rich element (ARE1) is important for regulation of degradation. ► UV cross-linking assays showed that a cytoplasmic protein of 80 kDa binds abundantly to ARE1 in response to CDCA-induced MAPK activation.