ArticleScience (New York, N.Y.)2020
The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation.
Article in Science (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 241 citations in OpenAlex.
- Canonical and non-canonical miRNA degradation shapes state transitions and stemness in breast cancer.The EMBO journal · 2026Article
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- Are RNA Therapies a Solid Foundation or a Frontier Yet to Be Conquered?International journal of molecular sciences · 2026Review
- Structural basis for RISC assembly of human Argonaute2.Molecular cell · 2026Article
- CLASHub is an integrated database and analytical platform for microRNA-target interactions.Nature communications · 2026Article
- A viral noncoding RNA is a master regulator of gene expression that defines host cell identity and function.Nucleic acids research · 2026Article
- A lncRNA drives developmentally timed decay of all members of an essential microRNA family.Genes & development · 2026Article
- Linking miRNAs to decay.Genes & development · 2026Article
- Article
- Targeting the TRIM25-AGO2-miR-148b-5p-ABCC1 axis overcomes chemoresistance in non-small cell lung cancer.Cell death & disease · 2026Article
- mRNA 3' UTRs direct microRNA degradation to participate in imprinted gene networks and regulate growth.Genes & development · 2026Article
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- Therapeutic microRNAs: Mechanisms, Delivery, and Clinical Translation in Oncology.International journal of molecular sciences · 2026Review
- High palmitate induces ferroptosis in RIN-m5f cells via miR-3584-5p-mediated suppression of AQP7.Scientific reports · 2026Article
- Article
- The E3 ubiquitin ligase mechanism specifying target-directed microRNA degradation.bioRxiv : the preprint server for biology · 2026Article
- Reprogramming tumor immunity through APOBEC3s-mediated mutagenesis: from genome instability to immune checkpoint interactions.Frontiers in immunology · 2026Review
- The pathophysiological role of MiRNAs in heart failure.Frontiers in cardiovascular medicine · 2026Review
- shRNAI: A deep neural network for the design of highly potent shRNAs.Molecular therapy. Nucleic acids · 2025Article
80 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
MicroRNAs (miRNAs) associate with Argonaute (AGO) proteins to direct widespread posttranscriptional gene repression. Although association with AGO typically protects miRNAs from nucleases, extensive pairing to some unusual target RNAs can trigger miRNA degradation. We found that this target-directed miRNA degradation (TDMD) required the ZSWIM8 Cullin-RING E3 ubiquitin ligase. This and other findings support a mechanistic model of TDMD in which target-directed proteolysis of AGO by the ubiquitin-proteasome pathway exposes the miRNA for degradation. Moreover, loss-of-function studies indicated that the ZSWIM8 Cullin-RING ligase accelerates degradation of numerous miRNAs in cells of mammals, flies, and nematodes, thereby specifying the half-lives of most short-lived miRNAs. These results elucidate the mechanism of TDMD and expand its inferred role in shaping miRNA levels in bilaterian animals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.