TY - JOUR
T1 - DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans.
AU - Suen, Kin Man
AU - Braukmann, Fabian
AU - Butler, Richard
AU - Bensaddek, Dalila
AU - Akay, Alper
AU - Lin, Chi-Chuan
AU - Milonaitytė, Dovilė
AU - Doshi, Neel
AU - Sapetschnig, Alexandra
AU - Lamond, Angus
AU - Ladbury, John Edward
AU - Miska, Eric Alexander
N1 - KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: We are grateful for the generous gifts of the DEPS-1
PY - 2020/8/27
Y1 - 2020/8/27
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10754/664937
UR - http://www.nature.com/articles/s41467-020-18089-1
UR - http://www.scopus.com/inward/record.url?scp=85089771119&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-18089-1
DO - 10.1038/s41467-020-18089-1
M3 - Article
C2 - 32843637
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
ER -