Journal Article

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

Becker, Kevin G., Zou, Sige, Xue, Yutong, Ku, Wai Lim, Zhao, Keji, De, Supriyo, Joo, Yuyoung, Lee, Seung Kyu, Shen, Weiping, Lehrmann, Elin, Ding, Yi, Chinen, Madoka, Ahmad, Muzammil, Sharov, Alexei, Wang, Weidong, Zhang, Yongqing, Lei, Elissa P.

2018

Overview

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. Topoisomerases solve topological problems during DNA metabolism, but their role in RNA metabolism remains unclear. Here the authors provide evidence that in Drosophila , Topoisomerase 3β interacts biochemically and genetically with the RNAi-induced silencing complex (RISC) to promote heterochromatin formation and transcriptional silencing.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/15 / 38/23 / 38/61 / 38/70 / 38/77 / 631/208/176/2016 / 631/208/505 / 631/337/100 / 631/45/173 / 64/24 / 82/51 / 82/58 / 82/83 / Animals / Argonaute 2 protein / Argonaute Proteins - genetics / Argonaute Proteins - metabolism / Catalysis / Catalytic activity / Chromosomal Proteins, Non-Histone - genetics / Chromosomal Proteins, Non-Histone - metabolism / DEAD-box RNA Helicases - genetics / DEAD-box RNA Helicases - metabolism / Deoxyribonucleic acid / DNA / DNA helicase / DNA topoisomerase IIIb / DNA Topoisomerases, Type I - genetics / DNA Topoisomerases, Type I - metabolism / Drosophila / Drosophila melanogaster - enzymology / Drosophila melanogaster - genetics / Drosophila melanogaster - metabolism / Drosophila Proteins - genetics / Drosophila Proteins - metabolism / Fragile X Mental Retardation Protein - genetics / Fragile X Mental Retardation Protein - metabolism / Gene expression / Gene silencing / Heterochromatin / Heterochromatin - genetics / Heterochromatin - metabolism / HP1 protein / Humanities and Social Sciences / Insects / Kinases / Metabolism / multidisciplinary / Mutants / Position-effect variegation / Protein Binding / Proteins / Ribonucleic acid / RNA / RNA helicase / RNA Interference / RNA, Small Interfering / RNA-Induced Silencing Complex - genetics / RNA-Induced Silencing Complex - metabolism / RNA-mediated interference / Science / Science (multidisciplinary) / siRNA / Variegation