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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 Z, 2018. "Topoisomerase 3β interacts with RNAi machinery to promote heterochromatin formation and transcriptional silencing in Drosophila," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07101-4
    DOI: 10.1038/s41467-018-07101-4
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    Cited by:

    1. Sourav Saha & Shar-yin Naomi Huang & Xi Yang & Liton Kumar Saha & Yilun Sun & Prashant Khandagale & Lisa M. Jenkins & Yves Pommier, 2023. "The TDRD3-USP9X complex and MIB1 regulate TOP3B homeostasis and prevent deleterious TOP3B cleavage complexes," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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