OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids

Veit Hornung; Rune Hartmann; Andrea Ablasser; Karl-Peter Hopfner

doi:10.1038/nri3719

OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids

Nat Rev Immunol. 2014 Aug;14(8):521-8. doi: 10.1038/nri3719. Epub 2014 Jul 18.

Authors

Veit Hornung¹, Rune Hartmann², Andrea Ablasser³, Karl-Peter Hopfner⁴

Affiliations

¹ Institute of Molecular Medicine, University Hospital, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
² Centre for Structural Biology, Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10c, 8000 Aarhus C, Denmark.
³ 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.
⁴ Department of Biochemistry and Gene Center, Ludwig-Maximilians-University, Feodor-Lynen-Strasse 25, D-81377 Munich, Germany.

PMID: 25033909
PMCID: PMC7097587
DOI: 10.1038/nri3719

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

2',5'-Oligoadenylate Synthetase / genetics
2',5'-Oligoadenylate Synthetase / immunology*
Adenine Nucleotides / genetics
Adenine Nucleotides / immunology
Cytosol / immunology*
Cytosol / virology
DNA / immunology*
Endoribonucleases / biosynthesis
Endoribonucleases / genetics
Humans
Immunity, Innate
Nucleotides, Cyclic / genetics
Nucleotidyltransferases / genetics
Nucleotidyltransferases / immunology*
Oligoribonucleotides / genetics
Oligoribonucleotides / immunology
RNA / immunology*
RNA Viruses / genetics
RNA Viruses / immunology
RNA, Viral / immunology
Second Messenger Systems / genetics
Second Messenger Systems / immunology
Viruses / immunology*

Substances

Adenine Nucleotides
Nucleotides, Cyclic
Oligoribonucleotides
RNA, Viral
cyclic guanosine monophosphate-adenosine monophosphate
2',5'-oligoadenylate
RNA
DNA
Nucleotidyltransferases
cGAS protein, human
2',5'-Oligoadenylate Synthetase
Endoribonucleases
2-5A-dependent ribonuclease

Abstract

Publication types

MeSH terms

Substances

Grants and funding