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

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...

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Autores principales: Suen, Kin Man, Braukmann, Fabian, Butler, Richard, Bensaddek, Dalila, Akay, Alper, Lin, Chi-Chuan, Milonaitytė, Dovilė, Doshi, Neel, Sapetschnig, Alexandra, Lamond, Angus, Ladbury, John Edward, Miska, Eric Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447803/
https://www.ncbi.nlm.nih.gov/pubmed/32843637
http://dx.doi.org/10.1038/s41467-020-18089-1
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author Suen, Kin Man
Braukmann, Fabian
Butler, Richard
Bensaddek, Dalila
Akay, Alper
Lin, Chi-Chuan
Milonaitytė, Dovilė
Doshi, Neel
Sapetschnig, Alexandra
Lamond, Angus
Ladbury, John Edward
Miska, Eric Alexander
author_facet Suen, Kin Man
Braukmann, Fabian
Butler, Richard
Bensaddek, Dalila
Akay, Alper
Lin, Chi-Chuan
Milonaitytė, Dovilė
Doshi, Neel
Sapetschnig, Alexandra
Lamond, Angus
Ladbury, John Edward
Miska, Eric Alexander
author_sort Suen, Kin Man
collection PubMed
description 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.
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spelling pubmed-74478032020-09-02 DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans Suen, Kin Man Braukmann, Fabian Butler, Richard Bensaddek, Dalila Akay, Alper Lin, Chi-Chuan Milonaitytė, Dovilė Doshi, Neel Sapetschnig, Alexandra Lamond, Angus Ladbury, John Edward Miska, Eric Alexander Nat Commun Article 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. Nature Publishing Group UK 2020-08-25 /pmc/articles/PMC7447803/ /pubmed/32843637 http://dx.doi.org/10.1038/s41467-020-18089-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Suen, Kin Man
Braukmann, Fabian
Butler, Richard
Bensaddek, Dalila
Akay, Alper
Lin, Chi-Chuan
Milonaitytė, Dovilė
Doshi, Neel
Sapetschnig, Alexandra
Lamond, Angus
Ladbury, John Edward
Miska, Eric Alexander
DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans
title DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans
title_full DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans
title_fullStr DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans
title_full_unstemmed DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans
title_short DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans
title_sort deps-1 is required for pirna-dependent silencing and piwi condensate organisation in caenorhabditis elegans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447803/
https://www.ncbi.nlm.nih.gov/pubmed/32843637
http://dx.doi.org/10.1038/s41467-020-18089-1
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