DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans

Kin Man Suen, Fabian Braukmann, Richard Butler, Dalila Bensaddek, Alper Akay, Chi-Chuan Lin, Dovilė Milonaitytė, Neel Doshi, Alexandra Sapetschnig, Angus Lamond, John Edward Ladbury and Eric Alexander Miska ()
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Kin Man Suen: University of Cambridge
Fabian Braukmann: University of Cambridge
Richard Butler: University of Cambridge
Dalila Bensaddek: University of Dundee
Alper Akay: University of Cambridge
Chi-Chuan Lin: University of Leeds, LC Miall Building
Dovilė Milonaitytė: University of Leeds, LC Miall Building
Neel Doshi: University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus
Alexandra Sapetschnig: Wellcome Trust Genome Campus
Angus Lamond: University of Dundee
John Edward Ladbury: University of Leeds, LC Miall Building
Eric Alexander Miska: University of Cambridge

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

Abstract: Abstract Membraneless organelles are sites for RNA biology including small non-coding RNA (ncRNA) mediated gene silencing. How small ncRNAs utilise phase separated environments for their function is unclear. We investigated how the PIWI-interacting RNA (piRNA) pathway engages with the membraneless organelle P granule in Caenorhabditis elegans. Proteomic analysis of the PIWI protein PRG-1 reveals an interaction with the constitutive P granule protein DEPS-1. DEPS-1 is not required for piRNA biogenesis but piRNA-dependent silencing: deps-1 mutants fail to produce the secondary endo-siRNAs required for the silencing of piRNA targets. We identify a motif on DEPS-1 which mediates a direct interaction with PRG-1. DEPS-1 and PRG-1 form intertwining clusters to build elongated condensates in vivo which are dependent on the Piwi-interacting motif of DEPS-1. Additionally, we identify EDG-1 as an interactor of DEPS-1 and PRG-1. Our study reveals how specific protein-protein interactions drive the spatial organisation and piRNA-dependent silencing within membraneless organelles.

Date: 2020
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DOI: 10.1038/s41467-020-18089-1

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