title: The RNA-binding protein HuR/ELAVL1 regulates IFN-β mRNA abundance and the type I IFN response.
abstract: Secretion of type I interferon (IFN) is the first cellular reaction to invading pathogens. Despite the protective function of these cytokines, an excessive response to their action can contribute to serious pathologies, such as autoimmune diseases. Transcripts of most cytokines contain adenylate-uridylate (A/U)-rich elements (AREs) that make them highly unstable. RNA-binding proteins (RBPs) are mediators of the regulatory mechanisms that determine the fate of mRNAs containing AREs. Here, we applied an affinity proteomic approach and identified lethal, abnormal vision, drosophila-like 1 (ELAVL1)/Hu antigen R (HuR) as the predominant RBP of the IFN-β mRNA ARE. Reduced expression or chemical inhibition of HuR severely hampered the type I IFN response in various cell lines and fibroblast-like synoviocytes isolated from joints of rheumatoid arthritis patients. These results define a role for HuR as a potent modulator of the type I IFN response. Taken together, HuR could be used as therapeutic target for diseases where type I IFN production is exaggerated.
authors: Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors: Barbara
authors: B
authors: Herdy
authors: Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.|Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Thomas
authors: T
authors: Karonitsch
authors: Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors: Gregory I
authors: GI
authors: Vladimer
authors: Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors: Chris S H
authors: CS
authors: Tan
authors: Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors: Alexey
authors: A
authors: Stukalov
authors: Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors: Claudia
authors: C
authors: Trefzer
authors: Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors: Johannes W
authors: JW
authors: Bigenzahn
authors: Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors: Tamara
authors: T
authors: Theil
authors: Department of Orthopedics, Medical University of Vienna, Vienna, Austria.
authors: Johannes
authors: J
authors: Holinka
authors: Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Hans P
authors: HP
authors: Kiener
authors: Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors: Jacques
authors: J
authors: Colinge
authors: Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors: Keiryn L
authors: KL
authors: Bennett
authors: Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors: Giulio
authors: G
authors: Superti-Furga
mesh_terms: D063307:AU Rich Elements; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D051959:ELAV Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D000067780:ELAV-Like Protein 1; D006367:HeLa Cells; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D007370:Interferon Type I / Q000096:biosynthesis*; D016899:Interferon-beta / Q000235:genetics*; D008969:Molecular Sequence Data; D011070:Poly I-C / Q000494:pharmacology; D055503:Protein Multimerization; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013583:Synovial Membrane / Q000276:immunology
chemical_list: D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D007369:Interferon Inducers; D007370:Interferon Type I; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016899:Interferon-beta; D011070:Poly I-C
keywords: A/U-rich elements (AREs); Cytokines; HuR/ELAVL1; Immune modulation; RNA-binding proteins; Type I interferon