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Updated: Jul 16, 2025

Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
Published on: July 27, 2022
KAT2 paralogs prevent dsRNA accumulation and interferon signaling to maintain intestinal stem cells
Mai-Uyen Nguyen1, Sarah Potgieter2, Winston Huang1
1Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ.
Abstract:
Histone acetyltransferases KAT2A and KAT2B are paralogs highly expressed in the intestinal epithelium, but their functions are not well understood. In this study, double knockout of murine Kat2 genes in the intestinal epithelium was lethal, resulting in robust activation of interferon signaling and interferon-associated phenotypes including the loss of intestinal stem cells. Use of pharmacological agents and sterile organoid cultures indicated a cell-intrinsic double-stranded RNA trigger for interferon signaling. Acetyl-proteomics and dsRIP-seq were employed to interrogate the mechanism behind this response, which identified mitochondria-encoded double-stranded RNA as the source of intrinsic interferon signaling. Kat2a and Kat2b therefore play an essential role in regulating mitochondrial functions as well as maintaining intestinal health.
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