Structural mechanism of R2D2 and Loqs-PD synergistic modulation on DmDcr-2 oligomers

Small interference RNAs are the key components of RNA interference, a conserved RNA silencing or viral defense mechanism in many eukaryotes. In Drosophila melanogaster , Dicer-2 ( Dm Dcr-2)-mediated RNAi pathway plays important roles in defending against viral infections and protecting genome integr...

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Bibliographic Details
Published in:Nature communications 2023-08, Vol.14 (1), p.5228-5228, Article 5228
Main Authors: Deng, Ting, Su, Shichen, Yuan, Xun, He, Jinqiu, Huang, Ying, Ma, Jinbiao, Wang, Jia
Format: Article
Language:English
Subjects:
101/28
631/337/505
631/45/500
631/535/1258/1259
Argonaute 2 protein
Cofactors
Depolymerization
DNA helicase
Double-stranded RNA
Eukaryotes
Fibers
Fruit flies
Genomes
Humanities and Social Sciences
Insects
Interference
multidisciplinary
Oligomers
RNA-mediated interference
Science
Science (multidisciplinary)
siRNA
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Summary:Small interference RNAs are the key components of RNA interference, a conserved RNA silencing or viral defense mechanism in many eukaryotes. In Drosophila melanogaster , Dicer-2 ( Dm Dcr-2)-mediated RNAi pathway plays important roles in defending against viral infections and protecting genome integrity. During the maturation of siRNAs, two cofactors can regulate Dm Dcr-2’s functions: Loqs-PD that is required for dsRNA processing, and R2D2 that is essential for the subsequent loading of siRNAs into effector Ago2 to form RISC complexes. However, due to the lack of structural information, it is still unclear whether R2D2 and Loqs-PD affect the functions of Dm Dcr-2 simultaneously. Here we present several cryo-EM structures of Dm Dcr-2/R2D2/Loqs-PD complex bound to dsRNAs with various lengths by the Helicase domain. These structures revealed that R2D2 and Loqs-PD can bind to different regions of Dm Dcr-2 without interfering with each other. Furthermore, the cryo-EM results demonstrate that these complexes can form large oligomers and assemble into fibers. The formation and depolymerization of these oligomers are associated with ATP hydrolysis. These findings provide insights into the structural mechanism of Dm Dcr-2 and its cofactors during siRNA processing. R2D2 and Loqs-PD are cofactors of Drosophila Dicer-2 (DmDcr-2), which generates siRNAs. Here the authors report the cryo-EM structures of DmDcr-2/R2D2/Loqs-PD with dsRNAs showing that these complexes can form oligomers and assemble into fibers.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-40919-1