Maternally inherited siRNAs initiate piRNA cluster formation
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1.
California Institute of Technology
Abstract
PIWI-interacting RNAs (piRNAs) guide transposable element repression in animal germ lines. In Drosophila, piRNAs are produced from heterochromatic loci, called piRNA clusters, which act as information repositories about genome invaders. piRNA generation by dual-strand clusters depends on the chromatin-bound Rhino-Deadlock-Cutoff (RDC) complex, which is deposited on clusters guided by piRNAs, forming a positive feedback loop in which piRNAs promote their own biogenesis. However, how piRNA clusters are formed before cognate piRNAs are present remains unknown. Here, we report spontaneous de novo piRNA cluster formation from repetitive transgenic sequences. Cluster formation occurs over several generations and requires continuous trans-generational maternal transmission of small RNAs. We discovered that maternally supplied small interfering RNAs (siRNAs) trigger de novo cluster activation in progeny. In contrast, siRNAs are dispensable for cluster function after its establishment. These results reveal an unexpected interplay between the siRNA and piRNA pathways and suggest a mechanism for de novo piRNA cluster formation triggered by siRNAs.
Copyright and License
© 2023 Elsevier.
Acknowledgement
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 to A.A.A. and R01 GM110217 to K.F.T.) and by the HHMI Faculty Scholar Award to A.A.A.
Contributions
Y.L., K.F.T., and A.A.A. designed the 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; and Y.L., K.F.T., and A.A.A. wrote the paper.
Data Availability
- Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
- The scripts and code are available on https://doi.org/10.5281/zenodo.8351702.
- Libraries generated from this study are deposited in GEO under accession codes GSE193091. Pol ll ChIP-seq data analyzed in this study were from Database: GSE4382947 and Database: GSE97719.16 The original images have been deposited at Mendeley Data: https://doi.org/10.17632/d65h9pttby.1.
Conflict of Interest
The authors declare no competing interests.
Additional details
- PMCID
- PMC10846595
- National Institutes of Health
- R01 GM097363
- National Institutes of Health
- R01 GM110217
- Howard Hughes Medical Institute
- Caltech groups
- Division of Biology and Biological Engineering, Tianqiao and Chrissy Chen Institute for Neuroscience