Topoisomerase 3β interacts with RNAi machinery to promote heterochromatin formation and transcriptional silencing in Drosophila

Seung Kyu Lee, Yutong Xue, Weiping Shen, Yongqing Zhang, Yuyoung Joo, Muzammil Ahmad, Madoka Chinen, Yi Ding, Wai Lim Ku, Supriyo De, Elin Lehrmann, Kevin G. Becker, Elissa P. Lei, Keji Zhao, Sige Zou, Alexei Sharov and Weidong Wang ()
Additional contact information
Seung Kyu Lee: National Institutes of Health
Yutong Xue: National Institutes of Health
Weiping Shen: National Institutes of Health
Yongqing Zhang: National Institutes of Health
Yuyoung Joo: National Institutes of Health
Muzammil Ahmad: National Institutes of Health
Madoka Chinen: National Institute of Diabetes and Digestive Kidney Diseases
Yi Ding: National Institutes of Health
Wai Lim Ku: National Institutes of Health
Supriyo De: National Institutes of Health
Elin Lehrmann: National Institutes of Health
Kevin G. Becker: National Institutes of Health
Elissa P. Lei: National Institute of Diabetes and Digestive Kidney Diseases
Keji Zhao: National Institutes of Health
Sige Zou: National Institutes of Health
Alexei Sharov: National Institutes of Health
Weidong Wang: National Institutes of Health

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: Abstract Topoisomerases solve topological problems during DNA metabolism, but whether they participate in RNA metabolism remains unclear. Top3β represents a family of topoisomerases carrying activities for both DNA and RNA. Here we show that in Drosophila, Top3β interacts biochemically and genetically with the RNAi-induced silencing complex (RISC) containing AGO2, p68 RNA helicase, and FMRP. Top3β and RISC mutants are similarly defective in heterochromatin formation and transcriptional silencing by position-effect variegation assay. Moreover, both Top3β and AGO2 mutants exhibit reduced levels of heterochromatin protein HP1 in heterochromatin. Furthermore, expression of several genes and transposable elements in heterochromatin is increased in the Top3β mutant. Notably, Top3β mutants defective in either RNA binding or catalytic activity are deficient in promoting HP1 recruitment and silencing of transposable elements. Our data suggest that Top3β may act as an RNA topoisomerase in siRNA-guided heterochromatin formation and transcriptional silencing.

Date: 2018
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DOI: 10.1038/s41467-018-07101-4

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