Innate immune sensing of nucleic acids provides resistance against viral infection and is important in the aetiology of autoimmune diseases. AGS (Aicardi–Goutières syndrome) is a monogenic autoinflammatory disorder mimicking in utero viral infection of the brain. Phenotypically and immunologically, it also exhibits similarities to SLE (systemic lupus erythaematosus). Three of the six genes identified to date encode components of the ribonuclease H2 complex. As all six encode enzymes involved in nucleic acid metabolism, it is thought that pathogenesis involves the accumulation of nucleic acids to stimulate an inappropriate innate immune response. Given that AGS is a monogenic disorder with a defined molecular basis, we use it as a model for common autoimmune disease to investigate cellular processes and molecular pathways responsible for nucleic-acid-mediated autoimmunity. These investigations have also provided fundamental insights into the biological roles of the RNase H2 endonuclease enzyme. In the present article, we describe how human RNase H2 and its role in AGS were first identified, and give an overview of subsequent structural, biochemical, cellular and developmental studies of this enzyme. These investigations have culminated in establishing this enzyme as a key genome-surveillance enzyme required for mammalian genome stability.
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Conference Article| August 11 2014
Ribonuclease H2 in health and disease
Martin A.M. Reijns;
Andrew P. Jackson
Andrew P. Jackson 1
*Medical Research Council Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, U.K.
1To whom correspondence should be addressed (email@example.com).
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Martin A.M. Reijns, Andrew P. Jackson; Ribonuclease H2 in health and disease. Biochem Soc Trans 1 August 2014; 42 (4): 717–725. doi: https://doi.org/10.1042/BST20140079
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