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GLH/VASA helicases promote germ granule formation to ensure the fidelity of piRNA-mediated transcriptome surveillance

Wenjun Chen, Jordan S Brown, Tao He, Wei-Sheng Wu, Shikui Tu, Zhiping Weng, Donglei Zhang, View ORCID ProfileHeng-Chi Lee
doi: https://doi.org/10.1101/2022.01.21.477267
Wenjun Chen
1Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA
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Jordan S Brown
1Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA
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Tao He
2Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Wei-Sheng Wu
3Department of Electrical Engineering, National Cheng Kung University, Tainan 701, Taiwan
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Shikui Tu
4Department of Computer Science and Engineering, Shanghai Jiao Tong University, Shanghai, China
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Zhiping Weng
5Department of Biochemistry and Molecular Biotechnology, University of Mass. Chan Medical School, Worcester, MA 01605 USA
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Donglei Zhang
2Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Heng-Chi Lee
1Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA
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  • ORCID record for Heng-Chi Lee
  • For correspondence: hengchilee@uchicago.edu
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ABSTRACT

The ability to distinguish non-self from self is the key characteristic for any defense system. piRNAs function as guardians of the genome by silencing non- self nucleic acids and transposable elements in animals. Many piRNA factors are enriched in perinuclear germ granules, but whether their localization is required for piRNA biogenesis or function is not known. Here we show that GLH/VASA helicase mutants exhibit defects in forming perinuclear condensates containing PIWI and other small RNA cofactors. These mutant animals produce largely normal levels of piRNA but are defective in triggering piRNA silencing. Strikingly, while many piRNA targets are activated in GLH mutants, we observed that hundreds of endogenous genes are aberrantly silenced by piRNAs. This defect in self versus non-self recognition was also observed in other mutants where perinuclear P granules are disrupted. Together, our results argue that perinuclear germ granules function critically to promote the fidelity of piRNA- based transcriptome surveillance in C. elegans and preserve self versus non-self distinction.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted January 22, 2022.
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GLH/VASA helicases promote germ granule formation to ensure the fidelity of piRNA-mediated transcriptome surveillance
Wenjun Chen, Jordan S Brown, Tao He, Wei-Sheng Wu, Shikui Tu, Zhiping Weng, Donglei Zhang, Heng-Chi Lee
bioRxiv 2022.01.21.477267; doi: https://doi.org/10.1101/2022.01.21.477267
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GLH/VASA helicases promote germ granule formation to ensure the fidelity of piRNA-mediated transcriptome surveillance
Wenjun Chen, Jordan S Brown, Tao He, Wei-Sheng Wu, Shikui Tu, Zhiping Weng, Donglei Zhang, Heng-Chi Lee
bioRxiv 2022.01.21.477267; doi: https://doi.org/10.1101/2022.01.21.477267

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