Active retrotransposons help maintain pericentromeric heterochromatin required for faithful cell division
- Yajing Hao1,2,3,5,
- Dongpeng Wang1,2,5,
- Shuheng Wu1,2,
- Xiao Li3,
- Changwei Shao3,
- Peng Zhang1,
- Jia-Yu Chen3,
- Do-Hwan Lim3,
- Xiang-Dong Fu3,
- Runsheng Chen1,2,4 and
- Shunmin He1,2
- 1Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, 100101, China;
- 2University of Chinese Academy of Sciences, Beijing, 100049, China;
- 3Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0651, USA;
- 4Guangdong Geneway Decoding Bio-Tech Corporation Limited, Foshan 528316, China
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↵5 These authors contributed equally to this work.
Abstract
Retrotransposons are populated in vertebrate genomes, and when active, are thought to cause genome instability with potential benefit to genome evolution. Retrotransposon-derived RNAs are also known to give rise to small endo-siRNAs to help maintain heterochromatin at their sites of transcription; however, as not all heterochromatic regions are equally active in transcription, it remains unclear how heterochromatin is maintained across the genome. Here, we address these problems by defining the origins of repeat-derived RNAs and their specific chromatin locations in Drosophila S2 cells. We demonstrate that repeat RNAs are predominantly derived from active gypsy elements and processed by Dcr-2 into small RNAs to help maintain pericentromeric heterochromatin. We also show in cultured S2 cells that synthetic repeat-derived endo-siRNA mimics are sufficient to rescue Dcr-2-deficiency-induced defects in heterochromatin formation in interphase and chromosome segregation during mitosis, demonstrating that active retrotransposons are required for stable genetic inheritance.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.256131.119.
- Received August 19, 2019.
- Accepted September 22, 2020.
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