Nature, Published online: 18 March 2026; doi:10.1038/s41586-026-10232-0

Target-directed microRNA degradation is driven by the atypical ZSWIM8–CUL3 E3 ubiquitin ligase that uses a two-RNA-factor authentication mechanism to specifically recognize AGO–miRNA–trigger RNA complexes and polyubiquitylate AGO.

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