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Suen, KM, Braukmann, F, Butler, R, Bensaddek, D, Akay, A 
ORCID: https://orcid.org/0000-0001-6825-4443, Lin, C. C, Doshi, N, Sapetschnig, A, Lamond, A, Ladbury, JE and Miska, EA
(2019)
Direct interaction of PIWI and DEPS-1 is essential for piRNA function and condensate ultrastructure in Caenorhabditis elegans.
Abstract
Membraneless organelles are platforms for many aspects of RNA biology including small non-coding RNA (ncRNA) mediated gene silencing. How small ncRNAs utilise phase separated environments for their function is unclear. To address this question, 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 revealed an interaction with the constitutive P granule protein DEPS-1. Furthermore we identified a novel motif on DEPS-1, PBS, which interacts directly with the Piwi domain of PRG-1. This protein complex forms intertwining ultrastructures to build elongated condensates in vivo. These sub-organelle ultrastructures depend on the Piwi-interacting motif of DEPS-1 and mediate piRNA function. Additionally, we identify a novel interactor of DEPS-1, EDG-1, which is required for DEPS-1 condensates to form correctly. We show that DEPS-1 is not required for piRNA biogenesis but piRNA function: deps-1 mutants fail to produce the secondary endo-siRNAs required for the silencing of piRNA targets. Our study reveals how specific protein-protein interactions drive the spatial organisation and function of small RNA pathways within membraneless organelles.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Science > Research Groups > Cells and Tissues |
| Depositing User: | LivePure Connector |
| Date Deposited: | 14 Oct 2019 14:30 |
| Last Modified: | 26 Jul 2023 09:38 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/72574 |
| DOI: | 10.1101/580043 |
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