Active retrotransposons help maintain pericentromeric heterochromatin required for faithful cell division

• 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
• Format: Article
• Language: English
• Subjects: Animals; Cell division; Cell Division - genetics; Centromere; Chromatin; Chromosome Segregation; Drosophila - genetics; Drosophila Proteins - genetics; Euchromatin; Genomes; Genomic instability; Heredity; Heterochromatin; High-Throughput Nucleotide Sequencing; Mitosis; Retroelements; Ribonuclease III - genetics; RNA Helicases - genetics; RNA, Small Interfering; siRNA; Transcription
• ISSN: 1088-9051; 1549-5469
• DOI: 10.1101/gr.256131.119

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.