RNA adenosine deaminase ADAR2 modulates T helper 17 cell effector function

Ma, S.; Cho, B. S.; Li, Y.; Abbasi, N.; Yee, B. A.; Sun, G.; Luo, C.; Chang, J. T.; Zhou, B.; Fu, X.-d.; Yeo, G. W.; Huang, W. J. M.

doi:10.1101/2020.09.22.308221

bioRxiv · 10.1101/2020.09.22.308221

RNA adenosine deaminase ADAR2 modulates T helper 17 cell effector function

Ma, S.·Cho, B. S.·Li, Y.·Abbasi, N.·Yee, B. A.·Sun, G.·Luo, C.·Chang, J. T.·Zhou, B.·Fu, X.-d.·Yeo, G. W.·Huang, W. J. M.

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Abstract

ADAR1 and ADAR2 catalyze adenosine-to-inosine (A-to-I) editing, the most common post-transcriptional modification in RNA. While ADAR1 is ubiquitously expressed and plays a critical role in preventing activation of the host immune system, ADAR2 exhibits tissue-specific and inducible expression patterns, and its function in the immune system is not known. Here, we identify an intragenic super-enhancer involved in the dramatic induction of ADAR2 when naive helper T cells differentiate toward the Th17 lineage. By editing the inverted repeat sequences at the 3 untranslated region (UTR) of Malt1, which encodes a component of the NF-{kappa}B activation complex, ADAR2 promotes MALT1 expression and Th17 effector function. Interference with the ADAR2-MALT1 pathway dampens the production of Th17 cytokines and promotes T cell-mediated colitis. This study expands our understanding of RNA editing in adaptive immunity and identifies the ADAR2-MALT1-IL-17A axis as a potential therapeutic target for inflammatory conditions in the intestine.

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Ma, S., Cho, B. S., Li, Y., Abbasi, N., Yee, B. A., Sun, G., Luo, C., Chang, J. T., Zhou, B., Fu, X.-d., Yeo, G. W., Huang, W. J. M.. 2020-09-22. RNA adenosine deaminase ADAR2 modulates T helper 17 cell effector function. https://doi.org/10.1101/2020.09.22.308221

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