+Search query
-Structure paper
| Title | DICER cleavage fidelity is governed by 5'-end binding pockets. |
|---|---|
| Journal, issue, pages | Nature, Year 2026 |
| Publish date | Mar 4, 2026 |
Authors | Minh Khoa Ngo / Cong Truc Le / Tuan Anh Nguyen / ![]() |
| PubMed Abstract | RNA interference (RNAi) depends on DICER, an essential enzyme that processes RNA precursors into small regulatory RNAs. DICER cleaves RNA precursors according to the 5'-end counting rule, in which ...RNA interference (RNAi) depends on DICER, an essential enzyme that processes RNA precursors into small regulatory RNAs. DICER cleaves RNA precursors according to the 5'-end counting rule, in which RNA length is measured from the 5'-end. Previous work proposed a single 5'-end binding pocket that disfavours guanosine (5'-G), leading to cleavage inaccuracies. Here we show that 5'-G promotes precise cleavage for many substrates. Using massively parallel dicing assays and cryo-electron microscopy, we identify a conserved guanosine-favoured (G-favoured) binding pocket in DICER, distinct from the previously described uridine-favoured (U-favoured) pocket. Together, these pockets influence the alignment between 21-nucleotide and 22-nucleotide cleavage registers, expanding the mechanism of small-RNA biogenesis in metazoan DICERs. We also find that conflicts between 5'-end binding and RNA-motif recognition can trigger RNA conformational adjustments that preserve accurate cleavage-site selection. In addition, conformational adjustments of the double-stranded RNA-binding domain (dsRBD) and PAZ domain help to align substrates with the catalytic centres for precise double-strand cleavage. These results show that the DICER cleavage mechanism integrates dual 5'-end binding pockets, RNA-motif influence and domain motions, advancing our understanding of microRNA biogenesis. |
External links | Nature / PubMed:41781616 |
| Methods | EM (single particle) |
| Resolution | 3.0 - 3.37 Å |
| Structure data | EMDB-64764, PDB-9v42: EMDB-64765, PDB-9v43: EMDB-67570, PDB-21cb: EMDB-67573, PDB-21cn: EMDB-67575, PDB-21cq: |
| Chemicals | ![]() ChemComp-CA: |
| Source |
|
Keywords | HYDROLASE/RNA / Endoribonuclease Dicer / RNA / miRNA / precursor miRNA / HYDROLASE / HYDROLASE-RNA complex / endonuclease / dicer |
Movie
Controller
Structure viewers
About Yorodumi Papers



Authors
External links










homo sapiens (human)
Keywords