biostudies-literatureUnknownLaVigne CANCI NIH HHSPrecise control of microRNA (miRNA) expression is critical during development. An important mechanism of miRNA regulation is target-directed microRNA degradation (TDMD), a pathway in which the binding of miRNAs to specialized trigger RNAs induces ubiquitylation and decay of associated Argonaute (AGO) proteins by the ZSWIM8 ubiquitin ligase. Concomitant release of miRNAs results in their rapid turnover. ZSWIM8-deficient mice exhibit reduced body size, cardiopulmonary and neurodevelopmental defects, and perinatal lethality. Despite widespread dysregulation of miRNAs in these animals, the vast majority of presumptive trigger RNAs that induce decay of ZSWIM8-regulated miRNAs remain undefined. Here, using AGO crosslinking and sequencing of hybrids (AGO-CLASH), a high-throughput method for identbioRxiv : the preprint server for biology2025.06.30.662380https://www.ebi.ac.uk/biostudies/studies/S-EPMC12236722biostudies-literature<i>Plagl1</i> and <i>Lrrc58</i> control mammalian body size by triggering target-directed microRNA degradation of miR-322 and miR-503.PMC12236722R01 CA282036Chang TCAcharya AEvers BMLaVigne CAZhang HMendell JTSethia KHan JCho SKim Mfalse<i>Plagl1</i> and <i>Lrrc58</i> control mammalian body size by triggering target-directed microRNA degradation of miR-322 and miR-503.Precise control of microRNA (miRNA) expression is critical during development. An important mechanism of miRNA regulation is target-directed microRNA degradation (TDMD), a pathway in which the binding of miRNAs to specialized trigger RNAs induces ubiquitylation and decay of associated Argonaute (AGO) proteins by the ZSWIM8 ubiquitin ligase. Concomitant release of miRNAs results in their rapid turnover. ZSWIM8-deficient mice exhibit reduced body size, cardiopulmonary and neurodevelopmental defects, and perinatal lethality. Despite widespread dysregulation of miRNAs in these animals, the vast majority of presumptive trigger RNAs that induce decay of ZSWIM8-regulated miRNAs remain undefined. Here, using AGO crosslinking and sequencing of hybrids (AGO-CLASH), a high-throughput method for ident2025-01-01T00:00:00Z2025 Jul2026-06-27T03:24:30.481Z2025-08-27T03:06:46.754ZS-EPMC122367224063111310.1101/2025.06.30.662380