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A hypoxia-responsive tRNA-derived small RNA confers renal protection via RNA autophagy

GSE295814 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2025/08/05 Platform GPL30173
Summary
Emerging studies have revealed diverse cellular functions of tRNA-derived small RNAs (tsRNAs, or tDRs). Here, we show that a hypoxia-induced tDR, derived from the 3’ end of tRNA-Asp-GTC (tRNA-Asp-GTC-3’tDR), activates, while its inhibition blocks autophagic flux in kidney cells. Functional gain/loss-of-function studies in murine kidney disease models demonstrate a significant reno-protective function of tRNA-Asp-GTC-3’tDR. Mechanistically, tRNA-Asp-GTC-3’tDR assembles stable G-quadruplex structures and sequesters pseudouridine synthase PUS7, preventing catalytic pseudouridylation of histone mRNAs. The resulting pseudouridylation deficiency directs histone mRNAs to the autophagosome-lysosome pathway, triggering RNA autophagy. We confirm this tDR-induced RNA autophagy pathway in murine and human kidney diseases. Together, our findings identify a novel role for tRNA-Asp-GTC-3’tDR in regulating RNA autophagy in kidney cells to maintain homeostasis and protect against kidney injury.
Published in
A hypoxia-responsive tRNA-derived small RNA confers renal protection through RNA autophagy
Li G, Sun L, Xin C et al. · Science (New York, N.Y.) 2025 · PMID 40674449 · doi:10.1126/science.adp5384
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Also filed as BioProject PRJNA1256427 and SRA study SRP581791. Searching any of these in the dataset finder brings you back here.

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