Deficient RNA Editing Implicated in Inflammatory Disease

Good news! This could be a new avenue of research!

"... One of the most common edits, which new research shows plays an important role in the onset of inflammatory disease, is the transformation of the nucleotide adenosine into inosine within a double-stranded RNA. A study published Wednesday (August 3) in Nature reveals that genetic variants that dampen this specific modification are associated with an increased risk of autoimmune and immune-mediated inflammatory disorders such as psoriasis, inflammatory bowel disease, and type 1 diabetes. ..."

From the abstract:

"A major challenge in human genetics is to identify the molecular mechanisms of trait-associated and disease-associated variants. ... However, despite successes, the molecular basis for a considerable fraction of trait-associated and disease-associated variants remains unclear. Here we show that ADAR-mediated adenosine-to-inosine RNA editing, a post-transcriptional event vital for suppressing cellular double-stranded RNA (dsRNA)-mediated innate immune interferon responses, is an important potential mechanism underlying genetic variants associated with common inflammatory diseases. We identified and characterized 30,319 cis-RNA editing QTLs (edQTLs) across 49 human tissues. These edQTLs were significantly enriched in genome-wide association study signals for autoimmune and immune-mediated diseases. Colocalization analysis of edQTLs with disease risk loci further pinpointed key, putatively immunogenic dsRNAs formed by expected inverted repeat Alu elements as well as unexpected, highly over-represented cis-natural antisense transcripts. Furthermore, inflammatory disease risk variants, in aggregate, were associated with reduced editing of nearby dsRNAs and induced interferon responses in inflammatory diseases. This unique directional effect agrees with the established mechanism that lack of RNA editing by ADAR1 leads to the specific activation of the dsRNA sensor MDA5 and subsequent interferon responses and inflammation. Our findings implicate cellular dsRNA editing and sensing as a previously underappreciated mechanism of common inflammatory diseases."

Deficient RNA Editing Implicated in Inflammatory Disease  | The Scientist Magazine® Genetic variants that reduce the editing levels of double-stranded RNA are associated with autoimmune and immune-mediated conditions, a study finds.

RNA editing underlies genetic risk of common inflammatory diseases (no public access)