Widespread inosine‐containing mRNA in lymphocytes regulated by ADAR1 in response to inflammation

Abstract

Adenosine‐to‐inosine (A‐to‐I) RNA editing is a post‐transcriptional modification of pre‐mRNA catalysed by an RNA‐specific adenosine deaminase (ADAR). A‐to‐I RNA editing has been previously reported in the pre‐mRNAs of brain glutamate and serotonin receptors and in lung tissue during inflammation. Here we report that systemic inflammation markedly induces inosine‐containing mRNA to approximately 5% of adenosine in total mRNA. Induction was the result of up‐regulation of A‐to‐I RNA editing as both dsRNA editing activity and ADAR1 expression were increased in the spleen, thymus and peripheral lymphocytes from endotoxin‐treated mice. Up‐regulation of ADAR1 was confirmed in vitro in T lymphocytes and macrophages stimulated with a variety of inflammatory mediators including tumour necrosis factor‐α and interferon‐γ. A late induction of RNA editing was detected in concanavalin A‐activated splenocytes stimulated with interleukin‐2 in vitro. Taken together, these data suggest that a large number of inosine‐containing mRNAs are produced during acute inflammation via up‐regulation of ADAR1‐mediated RNA editing. These events may affect the inflammatory and immune response through modulation of protein production.