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Autophagy

Regulation of autophagy by a tRNA-derived fragment

Nature Reviews Nephrology volume 21, page 649 (2025)Cite this article

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The cleavage of certain transfer RNAs (tRNAs) produces small tRNA-derived fragments (tDRs), which can contribute to cellular stress responses through processes such as the formation of stress granules or repression of RNA translation. Guoping Li and colleagues now demonstrate that a specific tDR derived from the 3′ end of tRNA-Asp-GTC — Asp-GTC-3′tDR — regulates RNA autophagy in kidney cells under basal conditions and as an adaptive response to hypoxic stress.

The researchers first identified Asp-GTC-3′tDR as the most upregulated tDR in HEK cells in response to hypoxia. Transfection of a synthetic Asp-GTC-3′tDR oligonucleotide into HEK cells induced autophagy, whereas inhibition of tDR function with use of a specific antisense oligonucleotide (ASO) inhibited autophagic flux.

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  1. Nature Reviews Nephrology http://www.nature.com/nrneph

    Susan J. Allison

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  1. Susan J. Allison
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Correspondence to Susan J. Allison.

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Allison, S.J. Regulation of autophagy by a tRNA-derived fragment. Nat Rev Nephrol 21, 649 (2025). https://doi.org/10.1038/s41581-025-01001-9

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