title: Chenodeoxycholic acid stabilization of LDL receptor mRNA depends on 3'-untranslated region and AU-rich element-binding protein.
abstract: 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 80kDa increasingly binds to the region including the ARE1 in response to CDCA-mediated MAPK activation.
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yashiro
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yokoi
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
authors.forename: Jun
authors.initials: J
authors.lastname: Inoue
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Sato
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D045744:Cell Line, Tumor; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D004789:Enzyme Activation; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D020871:RNA Stability / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D012333:RNA, Messenger; D011973:Receptors, LDL; D002635:Chenodeoxycholic Acid; D020929:Mitogen-Activated Protein Kinase Kinases