title: Phosphorylation of p40AUF1 regulates binding to A + U-rich mRNA-destabilizing elements and protein-induced changes in ribonucleoprotein structure.
abstract: Messenger RNA turnover directed by A + U-rich elements (AREs) involves selected ARE-binding proteins. Whereas several signaling systems may modulate ARE-directed mRNA decay and/or post-translationally modify specific trans-acting factors, it is unclear how these mechanisms are linked. In THP-1 monocytic leukemia cells, phorbol ester-induced stabilization of some mRNAs containing AREs was accompanied by dephosphorylation of Ser83 and Ser87 of polysome-associated p40AUF1. Here, we report that phosphorylation of p40AUF1 influences its ARE-binding affinity as well as the RNA conformational dynamics and global structure of the p40AUF1-ARE ribonucleoprotein complex. Most notably, association of unphosphorylated p40AUF1 induces a condensed RNA conformation upon ARE substrates. By contrast, phosphorylation of p40AUF1 at Ser83 and Ser87 inhibits this RNA structural transition. These data indicate that selective AUF1 phosphorylation may regulate ARE-directed mRNA turnover by remodeling local RNA structures, thus potentially altering the presentation of RNA and/or protein determinants involved in subsequent trans-factor recruitment.
authors.affiliation: Department of Biochemistry and Molecular Biology and Center for Fluorescence Spectroscopy, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. gwils001@umaryland.edu
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Wilson
authors.forename: Jiebo
authors.initials: J
authors.lastname: Lu
authors.forename: Kristina
authors.initials: K
authors.lastname: Sutphen
authors.forename: Yvelisse
authors.initials: Y
authors.lastname: Suarez
authors.forename: Smrita
authors.initials: S
authors.lastname: Sinha
authors.forename: Brandy
authors.initials: B
authors.lastname: Brewer
authors.forename: Eneida C
authors.initials: EC
authors.lastname: Villanueva-Feliciano
authors.forename: Riza M
authors.initials: RM
authors.lastname: Ysla
authors.forename: Sandy
authors.initials: S
authors.lastname: Charles
authors.forename: Gary
authors.initials: G
authors.lastname: Brewer
mesh_terms: D000595:Amino Acid Sequence; D016880:Anisotropy; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019281:Dimerization; D031541:Fluorescence Resonance Energy Transfer; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000737:chemistry* / Q000378:metabolism*; D006639:Histidine / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D015233:Models, Statistical; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D012261:Ribonucleoproteins / Q000737:chemistry*; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013816:Thermodynamics; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D009841:Oligonucleotides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; D012694:Serine; D006639:Histidine; D012313:RNA; D000071679:Glycogen Synthase Kinase 3 beta; D017868:Cyclic AMP-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3