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Active retrotransposons help maintain pericentromeric heterochromatin required for faithful cell division

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; h...

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Bibliographic Details
Published in:Genome research 2020-11, Vol.30 (11), p.1570-1582
Main Authors: Hao, Yajing, Wang, Dongpeng, Wu, Shuheng, Li, Xiao, Shao, Changwei, Zhang, Peng, Chen, Jia-Yu, Lim, Do-Hwan, Fu, Xiang-Dong, Chen, Runsheng, He, Shunmin
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Language:English
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Summary: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 S2 cells. We demonstrate that repeat RNAs are predominantly derived from active 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.
ISSN:1088-9051
1549-5469
DOI:10.1101/gr.256131.119