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, Eric Alexander Miska (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)
    88 Downloads (Pure)

    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.
    Original languageEnglish
    Article number4242
    Number of pages13
    JournalNature Communications
    Volume11
    Issue number1
    DOIs
    Publication statusPublished - 25 Aug 2020

    Keywords

    • Epigenetic memory
    • Gene silencing
    • Piwi RNAs
    • RNAi

    ASJC Scopus subject areas

    • General Physics and Astronomy
    • General Chemistry
    • General Biochemistry,Genetics and Molecular Biology

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