The RNA interference pathway: a new target for autoimmunity
Department of Biochemistry, Radboud University Nijmegen, Nijmegen, The Netherlands
Arthritis Research & Therapy 2006, 8:110 doi:10.1186/ar1987
See related research article by Jakymiw et al., http://arthritis-research.com/content/8/4/R87Published: 22 June 2006
Many intracellular macromolecular complexes that are involved in the production or degradation of RNAs are targeted by autoantibodies in systemic autoimmune diseases. RNA interference (RNAi) is a recently characterized gene silencing pathway by which specific mRNAs are either degraded or translationally suppressed. In a recent issue of Arthritis Research and Therapy, Andrew Jakymiw and colleagues reported that the enigmatic Su autoantigen complex contains key components of the RNAi machinery. Anti-Su autoantibodies from both human patients with rheumatic diseases and a mouse model of autoimmunity recognize the endonucleolytic Argonaute and Dicer proteins, both crucial enzymes of the RNAi pathway. These data raise the question of how the anti-Su response is triggered. So far, it is unknown whether molecular modifications may be involved, as has been proposed for other intracellular autoantigens. The implication of RNAi in anti-viral defence may suggest a role for virus infection in this process.