title: AU-rich elements in the 3'-UTR regulate the stability of the 141 amino acid isoform of parathyroid hormone-related protein mRNA.
abstract: We demonstrated previously that parathyroid hormone-related protein (PTHrP) 1-141 mRNA is the least stable of three isoforms and is the only isoform that is stabilized by TGF-β. In order to understand how PTHrP mRNA is stabilized by TGF-β, we first sought to elucidate the mechanism(s) that are responsible for the instability of PTHrP isoform 1-141 mRNA. The 3'-UTR of isoform 1-141 contains four AU-rich elements (AREs), which are known to mediate mRNA degradation. We utilized a luciferase reporter system to test whether these four AREs are responsible for the short half-life of PTHrP 1-141 mRNA. Our results demonstrated that ARE elements in the 3'-UTR of PTHrP 1-141 mRNA play a significant role in regulation of the stability of the mRNA. It is known that AREs mediate their effects on mRNA stability through a number of ARE-binding proteins that recruit the exosome, a complex of exonucleases that degrades the mRNA. We identified tristetraproline (TTP) as an RNA-binding protein that may be involved in ARE-mediated degradation of PTHrP 1-141 mRNA.
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, United States.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Luchin
authors.forename: Murali V P
authors.initials: MV
authors.lastname: Nadella
authors.forename: Nanda K
authors.initials: NK
authors.lastname: Thudi
authors.forename: Wessel P
authors.initials: WP
authors.lastname: Dirksen
authors.forename: Parul
authors.initials: P
authors.lastname: Gulati
authors.forename: Soledad A
authors.initials: SA
authors.lastname: Fernandez
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rosol
mesh_terms: D063307:AU Rich Elements; D001483:Base Sequence; D045744:Cell Line, Tumor; D063326:Exosome Multienzyme Ribonuclease Complex / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D006207:Half-Life; D006801:Humans; D008969:Molecular Sequence Data; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability / Q000187:drug effects; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D051816:Tristetraprolin / Q000235:genetics / Q000378:metabolism*
chemical_list: D044162:Parathyroid Hormone-Related Protein; D020033:Protein Isoforms; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D051816:Tristetraprolin; C497552:ZFP36 protein, human; D063326:Exosome Multienzyme Ribonuclease Complex