The E3 ubiquitin ligase mechanism specifying targeted microRNA degradation - PubMed
3 hours ago
- #microRNA
- #TDMD
- #ubiquitin ligase
- MicroRNAs (miRNAs) associate with Argonaute (AGO) proteins to regulate target RNAs.
- Target-directed miRNA degradation (TDMD) involves 'trigger' RNAs that down-regulate miRNAs.
- TDMD requires the cullin-RING E3 ligase, involving CUL3 and ZSWIM8 proteins.
- ZSWIM8-CUL3 E3 ligase mediates AGO binding and polyubiquitylation, key steps in TDMD.
- Cryogenic electron microscopy reveals ZSWIM8 recognizes specific AGO and RNA conformations shaped by miRNA-trigger pairing.
- The E3 ligase specificity involves RNA-RNA, RNA-protein, and protein-protein interactions, not a conventional degron.
- This mechanism establishes a two-RNA-factor authentication for protein ubiquitylation.