@article{63dfca34742747ad9aaacb1250be2788,
title = "DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans",
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.",
keywords = "Epigenetic memory, Gene silencing, Piwi RNAs, RNAi",
author = "{Man Suen}, Kin and Fabian Braukmann and Richard Butler and Dalila Bensaddek and Alper Akay and Chi-Chuan Lin and Dovilė Milonaitytė and Neel Doshi and Alexandra Sapetschnig and Angus Lamond and Ladbury, {John Edward} and Miska, {Eric Alexander}",
note = "Funding Information: We are grateful for the generous gifts of the DEPS-1::GFP and DEPS-1::RFP—expressing strains from the Seydoux Laboratory and the Mutator strains from the Ruvkun laboratory. We thank the Strome Laboratory for the anti-DEPS-1 antibody. RNAi-expression clones were kind gifts from the Ahringer laboratory. We are indebted to Dr. Nicola Lawrence from The Gurdon Institute Imaging Facility for her help in high-resolution imaging. This work was supported by the following grants to E.A.M.: Cancer Research UK (CRUK): C13474/A18583; CRUK C6946/A14492 and Wellcome Trust (Wellcome) grants 10460/Z/14/Z; Wellcome 092096/Z/10/Z; to J.E.L.: Cancer Research UK (CRUK): C57233/A22356. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). We thank Kay Harnish of the Gurdon Institute Sequencing Facility for managing the high-throughput sequencing. We thank Dr. Archana Yerra for her contribution to the editing for the manuscript. We thank Ms Claudia Flandoli for artwork in Fig. 5. Publisher Copyright: {\textcopyright} 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = aug,
day = "25",
doi = "10.1038/s41467-020-18089-1",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Research",
number = "1",
}