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KAT2A and KAT2B prevents double-stranded RNA formation and interferon signaling to maintain intestinal stem cell renewal

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 diminished H3K9ac expression, loss of stem cells, and robust activation of interferon signaling. 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 self-derived, 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.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Michael Verzi

PROVIDER: MSV000092370 | MassIVE | Fri Jul 07 07:11:00 BST 2023

REPOSITORIES: MassIVE

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