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DHX9 helicase promotes R-loop formation in cells with impaired RNA splicing

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  • Prasun Chakraborty

    (University of Dundee)

  • Jeffrey T. J. Huang

    (University of Dundee)

  • Kevin Hiom

    (University of Dundee)

Abstract

R-loops are stable nucleic acid structures that have important physiological functions, but which also pose a significant threat to genomic stability. Increased R-loops cause replication stress and chromosome fragility and have been associated with diseases such as neurodegeneration and cancer. Although excessive R-loops are a feature of cells that are defective in RNA processing, what causes them to form is unclear. Here, we demonstrate that DHX9 (RNA helicase A) promotes the formation of pathological and non-pathological R-loops. In the absence of splicing factors, formation of R-loops correlates with the prolonged association of DHX9 with RNA Polymerase II (RNA Pol II). This leads to the production of DNA–RNA hybrid, which traps RNA Pol II on chromatin with the potential to block DNA replication. Our data provide a molecular mechanism for the formation of R-loops that is relevant to neurodegenerative diseases and cancers in which deregulated RNA processing is a feature.

Suggested Citation

  • Prasun Chakraborty & Jeffrey T. J. Huang & Kevin Hiom, 2018. "DHX9 helicase promotes R-loop formation in cells with impaired RNA splicing," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06677-1
    DOI: 10.1038/s41467-018-06677-1
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    Cited by:

    1. Xingxing Ren & Qiuyuan Liu & Peirong Zhou & Tingyue Zhou & Decai Wang & Qiao Mei & Richard A. Flavell & Zhanju Liu & Mingsong Li & Wen Pan & Shu Zhu, 2024. "DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Bing-Ze Yang & Mei-Yin Liu & Kuan-Lin Chiu & Yuh-Ling Chien & Ching-An Cheng & Yu-Lin Chen & Li-Yu Tsui & Keng-Ru Lin & Hsueh-Ping Catherine Chu & Ching-Shyi Peter Wu, 2024. "DHX9 SUMOylation is required for the suppression of R-loop-associated genome instability," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Yan Wang & Binbin Ma & Xiaoxu Liu & Ge Gao & Zhuanzhuan Che & Menghan Fan & Siyan Meng & Xiru Zhao & Rio Sugimura & Hua Cao & Zhongjun Zhou & Jing Xie & Chengqi Lin & Zhuojuan Luo, 2022. "ZFP281-BRCA2 prevents R-loop accumulation during DNA replication," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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