Crystal structure of Drosophila Piwi

Sonomi Yamaguchi, Akira Oe, Kazumichi M. Nishida, Keitaro Yamashita, Asako Kajiya, Seiichi Hirano, Naoki Matsumoto, Naoshi Dohmae, Ryuichiro Ishitani, Kuniaki Saito, Haruhiko Siomi, Hiroshi Nishimasu (), Mikiko C. Siomi () and Osamu Nureki ()
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Sonomi Yamaguchi: The University of Tokyo
Akira Oe: The University of Tokyo
Kazumichi M. Nishida: The University of Tokyo
Keitaro Yamashita: The University of Tokyo
Asako Kajiya: The University of Tokyo
Seiichi Hirano: The University of Tokyo
Naoki Matsumoto: The University of Tokyo
Naoshi Dohmae: RIKEN Center for Sustainable Resource Science
Ryuichiro Ishitani: The University of Tokyo
Kuniaki Saito: Invertebrate Genetics Laboratory, National Institute of Genetics
Haruhiko Siomi: Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku
Hiroshi Nishimasu: The University of Tokyo
Mikiko C. Siomi: The University of Tokyo
Osamu Nureki: The University of Tokyo

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract PIWI-clade Argonaute proteins associate with PIWI-interacting RNAs (piRNAs), and silence transposons in animal gonads. Here, we report the crystal structure of the Drosophila PIWI-clade Argonaute Piwi in complex with endogenous piRNAs, at 2.9 Å resolution. A structural comparison of Piwi with other Argonautes highlights the PIWI-specific structural features, such as the overall domain arrangement and metal-dependent piRNA recognition. Our structural and biochemical data reveal that, unlike other Argonautes including silkworm Siwi, Piwi has a non-canonical DVDK tetrad and lacks the RNA-guided RNA cleaving slicer activity. Furthermore, we find that the Piwi mutant with the canonical DEDH catalytic tetrad exhibits the slicer activity and readily dissociates from less complementary RNA targets after the slicer-mediated cleavage, suggesting that the slicer activity could compromise the Piwi-mediated co-transcriptional silencing. We thus propose that Piwi lost the slicer activity during evolution to serve as an RNA-guided RNA-binding platform, thereby ensuring faithful co-transcriptional silencing of transposons.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14687-1

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DOI: 10.1038/s41467-020-14687-1

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