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Germ Granules Govern Small RNA Inheritance

In C. elegans nematodes, components of liquid-like germ granules were shown to be required for transgenerational small RNA inheritance. Surprisingly, we show here that mutants with defective germ granules can nevertheless inherit potent small RNA-based silencing responses, but some of the mutants lo...

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Autores principales: Lev, Itamar, Toker, Itai Antoine, Mor, Yael, Nitzan, Anat, Weintraub, Guy, Antonova, Olga, Bhonkar, Ornit, Ben Shushan, Itay, Seroussi, Uri, Claycomb, Julie M., Anava, Sarit, Gingold, Hila, Zaidel-Bar, Ronen, Rechavi, Oded
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739422/
https://www.ncbi.nlm.nih.gov/pubmed/31378614
http://dx.doi.org/10.1016/j.cub.2019.07.054
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author Lev, Itamar
Toker, Itai Antoine
Mor, Yael
Nitzan, Anat
Weintraub, Guy
Antonova, Olga
Bhonkar, Ornit
Ben Shushan, Itay
Seroussi, Uri
Claycomb, Julie M.
Anava, Sarit
Gingold, Hila
Zaidel-Bar, Ronen
Rechavi, Oded
author_facet Lev, Itamar
Toker, Itai Antoine
Mor, Yael
Nitzan, Anat
Weintraub, Guy
Antonova, Olga
Bhonkar, Ornit
Ben Shushan, Itay
Seroussi, Uri
Claycomb, Julie M.
Anava, Sarit
Gingold, Hila
Zaidel-Bar, Ronen
Rechavi, Oded
author_sort Lev, Itamar
collection PubMed
description In C. elegans nematodes, components of liquid-like germ granules were shown to be required for transgenerational small RNA inheritance. Surprisingly, we show here that mutants with defective germ granules can nevertheless inherit potent small RNA-based silencing responses, but some of the mutants lose this ability after many generations of homozygosity. Animals mutated in pptr-1, which is required for stabilization of P granules in the early embryo, display extraordinarily strong heritable RNAi responses, lasting for tens of generations. Intriguingly, the RNAi capacity of descendants derived from mutants defective in the core germ granule proteins MEG-3 and MEG-4 is determined by the genotype of the ancestors and changes transgenerationally. Further, whether the meg-3/4 mutant alleles were present in the paternal or maternal lineages leads to different transgenerational consequences. Small RNA inheritance, rather than maternal contribution of the germ granules themselves, mediates the transgenerational defects in RNAi of meg-3/4 mutants and their progeny. Accordingly, germ granule defects lead to heritable genome-wide mis-expression of endogenous small RNAs. Upon disruption of germ granules, hrde-1 mutants can inherit RNAi, although HRDE-1 was previously thought to be absolutely required for RNAi inheritance. We propose that germ granules sort and shape the RNA pool, and that small RNA inheritance maintains this activity for multiple generations.
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spelling pubmed-67394222019-09-16 Germ Granules Govern Small RNA Inheritance Lev, Itamar Toker, Itai Antoine Mor, Yael Nitzan, Anat Weintraub, Guy Antonova, Olga Bhonkar, Ornit Ben Shushan, Itay Seroussi, Uri Claycomb, Julie M. Anava, Sarit Gingold, Hila Zaidel-Bar, Ronen Rechavi, Oded Curr Biol Article In C. elegans nematodes, components of liquid-like germ granules were shown to be required for transgenerational small RNA inheritance. Surprisingly, we show here that mutants with defective germ granules can nevertheless inherit potent small RNA-based silencing responses, but some of the mutants lose this ability after many generations of homozygosity. Animals mutated in pptr-1, which is required for stabilization of P granules in the early embryo, display extraordinarily strong heritable RNAi responses, lasting for tens of generations. Intriguingly, the RNAi capacity of descendants derived from mutants defective in the core germ granule proteins MEG-3 and MEG-4 is determined by the genotype of the ancestors and changes transgenerationally. Further, whether the meg-3/4 mutant alleles were present in the paternal or maternal lineages leads to different transgenerational consequences. Small RNA inheritance, rather than maternal contribution of the germ granules themselves, mediates the transgenerational defects in RNAi of meg-3/4 mutants and their progeny. Accordingly, germ granule defects lead to heritable genome-wide mis-expression of endogenous small RNAs. Upon disruption of germ granules, hrde-1 mutants can inherit RNAi, although HRDE-1 was previously thought to be absolutely required for RNAi inheritance. We propose that germ granules sort and shape the RNA pool, and that small RNA inheritance maintains this activity for multiple generations. Cell Press 2019-09-09 /pmc/articles/PMC6739422/ /pubmed/31378614 http://dx.doi.org/10.1016/j.cub.2019.07.054 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Lev, Itamar
Toker, Itai Antoine
Mor, Yael
Nitzan, Anat
Weintraub, Guy
Antonova, Olga
Bhonkar, Ornit
Ben Shushan, Itay
Seroussi, Uri
Claycomb, Julie M.
Anava, Sarit
Gingold, Hila
Zaidel-Bar, Ronen
Rechavi, Oded
Germ Granules Govern Small RNA Inheritance
title Germ Granules Govern Small RNA Inheritance
title_full Germ Granules Govern Small RNA Inheritance
title_fullStr Germ Granules Govern Small RNA Inheritance
title_full_unstemmed Germ Granules Govern Small RNA Inheritance
title_short Germ Granules Govern Small RNA Inheritance
title_sort germ granules govern small rna inheritance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739422/
https://www.ncbi.nlm.nih.gov/pubmed/31378614
http://dx.doi.org/10.1016/j.cub.2019.07.054
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