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

Sonomi Yamaguchi, Masahiro Naganuma, Tomohiro Nishizawa, Tsukasa Kusakizako, Yukihide Tomari (), Hiroshi Nishimasu () and Osamu Nureki ()
Additional contact information
Sonomi Yamaguchi: The University of Tokyo
Masahiro Naganuma: RIKEN Center for Biosystems Dynamics Research
Tomohiro Nishizawa: Yokohama City University, Graduate School of Medical Science
Tsukasa Kusakizako: The University of Tokyo
Yukihide Tomari: The University of Tokyo
Hiroshi Nishimasu: The University of Tokyo
Osamu Nureki: The University of Tokyo

Nature, 2022, vol. 607, issue 7918, 393-398

Abstract: Abstract In flies, Argonaute2 (Ago2) and small interfering RNA (siRNA) form an RNA-induced silencing complex to repress viral transcripts1. 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 orientation2–5. 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.

Date: 2022
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41586-022-04790-2 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:607:y:2022:i:7918:d:10.1038_s41586-022-04790-2

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-022-04790-2

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().