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RNA structure probing reveals the structural basis of Dicer binding and cleavage

Author

Listed:
  • Qing-Jun Luo

    (Stanford University
    Stanford University)

  • Jinsong Zhang

    (Ministry of Education Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University
    Tsinghua-Peking Center for Life Sciences)

  • Pan Li

    (Ministry of Education Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University
    Tsinghua-Peking Center for Life Sciences)

  • Qing Wang

    (Stanford University
    Stanford University
    Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-Sen University)

  • Yue Zhang

    (Stanford University
    Stanford University
    Freenome Holdings Inc.)

  • Biswajoy Roy-Chaudhuri

    (Stanford University
    Stanford University
    Impossible Foods Inc.)

  • Jianpeng Xu

    (Stanford University
    Stanford University)

  • Mark A. Kay

    (Stanford University
    Stanford University)

  • Qiangfeng Cliff Zhang

    (Ministry of Education Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University
    Tsinghua-Peking Center for Life Sciences)

Abstract

It is known that an RNA’s structure determines its biological function, yet current RNA structure probing methods only capture partial structure information. The ability to measure intact (i.e., full length) RNA structures will facilitate investigations of the functions and regulation mechanisms of small RNAs and identify short fragments of functional sites. Here, we present icSHAPE-MaP, an approach combining in vivo selective 2′-hydroxyl acylation and mutational profiling to probe intact RNA structures. We further showcase the RNA structural landscape of substrates bound by human Dicer based on the combination of RNA immunoprecipitation pull-down and icSHAPE-MaP small RNA structural profiling. We discover distinct structural categories of Dicer substrates in correlation to both their binding affinity and cleavage efficiency. And by tertiary structural modeling constrained by icSHAPE-MaP RNA structural data, we find the spatial distance measuring as an influential parameter for Dicer cleavage-site selection.

Suggested Citation

  • Qing-Jun Luo & Jinsong Zhang & Pan Li & Qing Wang & Yue Zhang & Biswajoy Roy-Chaudhuri & Jianpeng Xu & Mark A. Kay & Qiangfeng Cliff Zhang, 2021. "RNA structure probing reveals the structural basis of Dicer binding and cleavage," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23607-w
    DOI: 10.1038/s41467-021-23607-w
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    Cited by:

    1. Shurong Liu & Junhong Huang & Jie Zhou & Siyan Chen & Wujian Zheng & Chang Liu & Qiao Lin & Ping Zhang & Di Wu & Simeng He & Jiayi Ye & Shun Liu & Keren Zhou & Bin Li & Lianghu Qu & Jianhua Yang, 2024. "NAP-seq reveals multiple classes of structured noncoding RNAs with regulatory functions," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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