title: A novel RNA molecular signature for activation of 2'-5' oligoadenylate synthetase-1.
abstract: Human 2'-5' oligoadenylate synthetase-1 (OAS1) is central in innate immune system detection of cytoplasmic double-stranded RNA (dsRNA) and promotion of host antiviral responses. However, the molecular signatures that promote OAS1 activation are currently poorly defined. We show that the 3'-end polyuridine sequence of viral and cellular RNA polymerase III non-coding transcripts is critical for their optimal activation of OAS1. Potentiation of OAS1 activity was also observed with a model dsRNA duplex containing an OAS1 activation consensus sequence. We determined that the effect is attributable to a single appended 3'-end residue, is dependent upon its single-stranded nature with strong preference for pyrimidine residues and is mediated by a highly conserved OAS1 residue adjacent to the dsRNA binding surface. These findings represent discovery of a novel signature for OAS1 activation, the 3'-single-stranded pyrimidine (3'-ssPy) motif, with potential functional implications for OAS1 activity in its antiviral and other anti-proliferative roles.
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA Microbiology and Molecular Genetics (MMG) Program, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Virginia K
authors.initials: VK
authors.lastname: Vachon
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA Biochemistry, Cell and Developmental Biology (BCDB) Program, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Calderon
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA gconn@emory.edu.
authors.forename: Graeme L
authors.identifier: http://orcid.org/0000-0002-2419-380X
authors.initials: GL
authors.lastname: Conn
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D016296:Mutagenesis; D059372:Nucleotide Motifs; D011743:Pyrimidines / Q000032:analysis; D012330:RNA, Double-Stranded / Q000378:metabolism; D022661:RNA, Untranslated / Q000737:chemistry / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011743:Pyrimidines; D012330:RNA, Double-Stranded; D022661:RNA, Untranslated; D012367:RNA, Viral; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase