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RPA transforms RNase H1 to a bidirectional exoribonuclease for processive RNA–DNA hybrid cleavage

Author

Listed:
  • Yanan Li

    (ShanghaiTech University)

  • Chao Liu

    (Guangzhou Medical University
    Chinese Academy of Sciences)

  • Xinshuo Jia

    (ShanghaiTech University)

  • Lulu Bi

    (ShanghaiTech University)

  • Zhiyun Ren

    (ShanghaiTech University
    University of Chinese Academy of Sciences)

  • Yilin Zhao

    (ShanghaiTech University)

  • Xia Zhang

    (ShanghaiTech University)

  • Lijuan Guo

    (ShanghaiTech University)

  • Yanling Bao

    (ShanghaiTech University)

  • Cong Liu

    (Chinese Academy of Sciences)

  • Wei Li

    (Guangzhou Medical University
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Bo Sun

    (ShanghaiTech University)

Abstract

RNase H1 has been acknowledged as an endoribonuclease specializing in the internal degradation of the RNA moiety within RNA–DNA hybrids, and its ribonuclease activity is indispensable in multifaceted aspects of nucleic acid metabolism. However, the molecular mechanism underlying RNase H1-mediated hybrid cleavage remains inadequately elucidated. Herein, using single-molecule approaches, we probe the dynamics of the hybrid cleavage by Saccharomyces cerevisiae RNase H1. Remarkably, a single RNase H1 enzyme displays 3′-to-5′ exoribonuclease activity. The directional RNA degradation proceeds processively and yet discretely, wherein unwinding approximately 6-bp hybrids as a prerequisite for two consecutive 3-nt RNA excisions limits the overall rate within each catalytic cycle. Moreover, Replication Protein A (RPA) reinforces RNase H1’s 3′-to-5′ nucleolytic rate and processivity and stimulates its 5′-to-3′ exoribonuclease activity. This stimulation is primarily realized through the pre-separation of the hybrids and consequently transfers RNase H1 to a bidirectional exoribonuclease, further potentiating its cleavage efficiency. These findings unveil unprecedented characteristics of an RNase and provide a dynamic view of RPA-enhanced processive hybrid cleavage by RNase H1.

Suggested Citation

  • Yanan Li & Chao Liu & Xinshuo Jia & Lulu Bi & Zhiyun Ren & Yilin Zhao & Xia Zhang & Lijuan Guo & Yanling Bao & Cong Liu & Wei Li & Bo Sun, 2024. "RPA transforms RNase H1 to a bidirectional exoribonuclease for processive RNA–DNA hybrid cleavage," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51984-5
    DOI: 10.1038/s41467-024-51984-5
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    References listed on IDEAS

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    1. Xiao-Wen Yang & Xiao-Peng Han & Chong Han & James London & Richard Fishel & Jiaquan Liu, 2022. "MutS functions as a clamp loader by positioning MutL on the DNA during mismatch repair," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
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