7V6C

Structure of the Dicer-2-R2D2 heterodimer bound to small RNA duplex

Summary for 7V6C

• Entry DOI: 10.2210/pdb7v6c/pdb
• Related: 7V6B
• EMDB information: 31742
• Descriptor: Dicer-2, isoform A, R2D2, RNA (5'-R(P*UP*GP*AP*GP*G)-3'), ... (6 entities in total)
• Functional Keywords: rna binding protein, ribonuclease, double-stranded rna-binding protein
• Biological source: Drosophila melanogaster (Fruit fly); More
• Total number of polymer chains: 6
• Total formula weight: 266517.63

Authors

Yamaguchi, S.,Nishizawa, T.,Kusakizako, T.,Yamashita, K.,Tomita, A.,Hirano, H.,Nishimasu, H.,Nureki, O. (deposition date: 2021-08-20, release date: 2022-03-23, Last modification date: 2024-06-12)

Primary citation

Yamaguchi, S.,Naganuma, M.,Nishizawa, T.,Kusakizako, T.,Tomari, Y.,Nishimasu, H.,Nureki, O.
Structure of the Dicer-2-R2D2 heterodimer bound to a small RNA duplex.
Nature, 607:393-398, 2022

PubMed Abstract: In flies, Argonaute2 (Ago2) and small interfering RNA (siRNA) form an RNA-induced silencing complex to repress viral transcripts. The RNase III enzyme Dicer-2 associates with its partner protein R2D2 and cleaves long double-stranded RNAs to produce 21-nucleotide siRNA duplexes, which are then loaded into Ago2 in a defined orientation. Here we report cryo-electron microscopy structures of the Dicer-2-R2D2 and Dicer-2-R2D2-siRNA complexes. R2D2 interacts with the helicase domain and the central linker of Dicer-2 to inhibit the promiscuous processing of microRNA precursors by Dicer-2. Notably, our structure represents the strand-selection state in the siRNA-loading process, and reveals that R2D2 asymmetrically recognizes the end of the siRNA duplex with the higher base-pairing stability, and the other end is exposed to the solvent and is accessible by Ago2. Our findings explain how R2D2 senses the thermodynamic asymmetry of the siRNA and facilitates the siRNA loading into Ago2 in a defined orientation, thereby determining which strand of the siRNA duplex is used by Ago2 as the guide strand for target silencing.

PubMed: 35768503
DOI: 10.1038/s41586-022-04790-2

Experimental method

ELECTRON MICROSCOPY (3.3 Å)