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, Osamu Nureki

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number858
JournalNature communications
Volume11
Issue number1
DOIs
Publication statusPublished - 2020 Dec 1

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Yamaguchi, S., Oe, A., Nishida, K. M., Yamashita, K., Kajiya, A., Hirano, S., Matsumoto, N., Dohmae, N., Ishitani, R., Saito, K., Siomi, H., Nishimasu, H., Siomi, M. C., & Nureki, O. (2020). Crystal structure of Drosophila Piwi. Nature communications, 11(1), [858]. https://doi.org/10.1038/s41467-020-14687-1