Life Sciences Seminar Series: RNA and immunity: how does the cell discriminate self from non-self RN

• 19 February 2015
• Seminar room 114, pavilion A11, University Campus Bohunice, Brno

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Modication of nucleic acids is often employed in innate immunity to help discriminate ‘self’ from ‘non self’, one example being the use of restriction enzymes in bacteria. However the role of RNA modication in innate immunity is poorly understood. We have found that mutation in the human RNA editing/RNA modifying enzyme ADAR1 can cause Aicardi-Goutieres Syndrome (AGS) 1 which is an autoimmune disorder. Recently we have rescued the embryonic lethality to birth by generating a double homozygous mutant with Adar1 and another mutant in the innate immune pathway 2. We propose that ADAR1 plays a major role in the regulation of endogenous cellular dsRNAs and in the absence of ADAR1, cellular RNAs aberrantly stimulate an innate immune response which leads to autoimmune disease phenotypes.

1. Rice, G.I. et al. Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature. Nat Genet 44, 1243-8 (2012).

2. Mannion N. et al. The RNA editing enzyme ADAR1 is a key component of innate
immune responses to RNA. Cell Reports 9, 1482-9 (2014).