title: OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids.
abstract: Recent discoveries in the field of innate immunity have highlighted the existence of a family of nucleic acid-sensing proteins that have similar structural and functional properties. These include the well-known oligoadenylate synthase (OAS) family proteins and the recently identified OAS homologue cyclic GMP-AMP (cGAMP) synthase (cGAS). The OAS proteins and cGAS are template-independent nucleotidyltransferases that, once activated by double-stranded nucleic acids in the cytosol, produce unique classes of 2'-5'-linked second messenger molecules, which - through distinct mechanisms - have crucial antiviral functions. 2'-5'-linked oligoadenylates limit viral propagation through the activation of the enzyme RNase L, which degrades host and viral RNA, and 2'-5'-linked cGAMP activates downstream signalling pathways to induce de novo antiviral gene expression. In this Progress article, we describe the striking functional and structural similarities between OAS proteins and cGAS, and highlight their roles in antiviral immunity.
authors.affiliation: Institute of Molecular Medicine, University Hospital, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Veit
authors.initials: V
authors.lastname: Hornung
authors.affiliation: Centre for Structural Biology, Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10c, 8000 Aarhus C, Denmark.
authors.forename: Rune
authors.initials: R
authors.lastname: Hartmann
authors.affiliation: Institute of Molecular Medicine, University Hospital, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany, and the Global Health Institute, École Polytechnique Fédérale de Lausanne, Station 15, CH-1015 Lausanne, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ablasser
authors.affiliation: Department of Biochemistry and Gene Center, Ludwig-Maximilians-University, Feodor-Lynen-Strasse 25, D-81377 Munich, Germany.
authors.forename: Karl-Peter
authors.initials: KP
authors.lastname: Hopfner
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000276:immunology*; D000227:Adenine Nucleotides / Q000235:genetics / Q000276:immunology; D003600:Cytosol / Q000276:immunology* / Q000821:virology; D004247:DNA / Q000276:immunology*; D004722:Endoribonucleases / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate; D009712:Nucleotides, Cyclic / Q000235:genetics; D009713:Nucleotidyltransferases / Q000235:genetics / Q000276:immunology*; D009843:Oligoribonucleotides / Q000235:genetics / Q000276:immunology; D012313:RNA / Q000276:immunology*; D012328:RNA Viruses / Q000235:genetics / Q000276:immunology; D012367:RNA, Viral / Q000276:immunology; D015290:Second Messenger Systems / Q000235:genetics / Q000276:immunology; D014780:Viruses / Q000276:immunology*; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D015088:2',5'-Oligoadenylate Synthetase; D000227:Adenine Nucleotides; D004247:DNA; D004722:Endoribonucleases; D009712:Nucleotides, Cyclic; D009713:Nucleotidyltransferases; D009843:Oligoribonucleotides; D012313:RNA; D012367:RNA, Viral; C584311:cyclic guanosine monophosphate-adenosine monophosphate; C023505:2',5'-oligoadenylate; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase; C031956:2-5A-dependent ribonuclease