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TRF-Glu-TTC exacerbates intestinal ischemia/reperfusion injury via ADAR1/autophagy/ROS/necroptosis signaling axis

ABSTRACT: Using tRNA-derived stress-induced RNA (tiRNA) and tRNA-derived fragment (tRF) sequencing, we identified tRF-Glu-TTC as significantly upregulated in intestinal tissues, plasma, epithelial cells, and human clinical samples. tRF-Glu-TTC levels positively correlated with the severity of intestinal injury. Functionally, tRF-Glu-TTC exacerbates intestinal mucosal damage by activating TNF pathway-mediated necroptosis in intestinal epithelial cells. Mechanistically, tRF-Glu-TTC directly binds to and suppresses the RNA-editing enzyme ADAR1, impairing adenosine-to-inosine editing of autophagy-related transcripts (ATG18 and Lamp2), thereby suppressing autophagy and concurrently triggering reactive oxygen species (ROS) accumulation. This cascade promoted TNF-α secretion, amplifying TNF pathway-mediated necroptosis.

ORGANISM(S): Mus Musculus

SUBMITTER: Kexuan Liu

PROVIDER: PXD069515 | iProX | Thu Oct 16 00:00:00 BST 2025

REPOSITORIES: iProX

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