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Maternally inherited siRNAs initiate piRNA cluster formation

Luo, Yicheng and He, Peng and Kanrar, Nivedita and Fejes Toth, Katalin and Aravin, Alexei A. (2022) Maternally inherited siRNAs initiate piRNA cluster formation. . (Unpublished)

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PIWI-interacting RNAs (piRNAs) guide repression of transposable elements in germlines of animals. In Drosophila, piRNAs are produced from heterochromatic genomic loci, called piRNA clusters, that act as a repositories of information about genome invaders. piRNA generation by dual-strand clusters depend on the chromatin-bound Rhino-Deadlock-Cutoff (RDC) complex, which is deposited on clusters guided by piRNAs, forming a feed-forward loop in which piRNAs promote their own biogenesis. However, how piRNA clusters are formed initially, before cognate piRNAs are present, remained unknown. Here we report spontaneous de novo formation of a piRNA cluster from repetitive transgenic sequences. We show that cluster formation occurs gradually over several generations and requires continuous trans-generational transmission of small RNAs from mothers to their progeny. We discovered that maternally-supplied siRNAs are responsible for triggering de novo cluster activation in progeny. In contrast, the siRNA pathway is dispensable for cluster function after its establishment. These results revealed an unexpected cross-talk between the siRNA and piRNA pathways and suggest a mechanism for de novo formation of piRNA clusters triggered by production of siRNAs.

Item Type:Report or Paper (Discussion Paper)
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URLURL TypeDescription Paper Itemscripts
Luo, Yicheng0000-0003-3704-2389
Fejes Toth, Katalin0000-0001-6558-2636
Aravin, Alexei A.0000-0002-6956-8257
Additional Information: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-ND 4.0 International license. We thank members of the Aravin and Fejes Toth labs for discussion and comments. We thank Julius Brennecke for providing the Rhino antibody. We thank Igor Antoshechkin (Caltech) for help with sequencing. This work was supported by grants from the National Institutes of Health (R01 GM097363) and by the HHMI Faculty Scholar Award to AAA. Author Contributions. Y.L., K.F.T. and A.A.A. designed experiments. Y.L. performed all experiments; N.K. helped to perform imaging and ChIP experiments; P.H. performed the computational analysis; Y.L. and P.H. analyzed the data; Y.L., K.F.T. and A.A.A. wrote the paper. Data availability Libraries generated from this study are deposited in GEO under accession codes GSE193091. The scripts are available on GitHub: Pol ll ChIP-seq data analyzed in this study were from GSE43829 (Le Thomas et al., 2013) and GSE97719 (Andersen et al., 2017). The authors have declared no competing interest.
Funding AgencyGrant Number
NIHR01 GM097363
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Record Number:CaltechAUTHORS:20220210-639875000
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Official Citation:Maternally inherited siRNAs initiate piRNA cluster formation Yicheng Luo, Peng He, Nivedita Kanrar, Katalin Fejes Toth, Alexei Aravin bioRxiv 2022.02.08.479612; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:113377
Deposited By: George Porter
Deposited On:10 Feb 2022 18:57
Last Modified:10 Feb 2022 18:57

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