Induction of inosine containing mRNA during the inflamma-tory stress in C57BL/6 mouse

Abstract

A-to-I RNA editing is a recently discovered process of post-transcription modification of premRNA by adenosine deamination that results in the production of proteins not inherent in the genome. The present study aimed to identify a role for A-to-I RNA editing in the acute inflammation. It was found that A-to-I edtiting activities of RNA editases, ADARs, were upregulated in lung, spleen, thymus and lymph node of mouse during endotoxin stimulation. Importantly, the number of inosine in poly(A) RNA isolated from mouse lung and spleen was significantly increased in correlating with the induction of ADARs’ editing activity. The in vitro synthesized RNA which did not contain inosine was edited by thymus extracts and the generation of inosine was greatly increased after editing in LPS treated thymus extract. Take together, these data suggest that A-to-I RNA editing by ADARs may play an important role in pathogenesis of inflammation. The existence of high level of I-mRNA also suggests that more protein isoforms might be generated from a single gene via adenosine deamination by ADARs during inflammatory stress.