IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36489-x.html
   My bibliography  Save this article

Mechanisms of the RNA helicases DDX42 and DDX46 in human U2 snRNP assembly

Author

Listed:
  • Fenghua Yang

    (Fudan University
    Westlake University; Institute of Biology, Westlake Institute for Advanced Study
    Westlake Laboratory of Life Sciences and Biomedicine)

  • Tong Bian

    (Fudan University
    Westlake University; Institute of Biology, Westlake Institute for Advanced Study
    Westlake Laboratory of Life Sciences and Biomedicine)

  • Xiechao Zhan

    (Westlake University; Institute of Biology, Westlake Institute for Advanced Study
    Westlake Laboratory of Life Sciences and Biomedicine)

  • Zhe Chen

    (School of Basic Medical Sciences, Xinjiang Medical University)

  • Zhihan Xing

    (Westlake University; Institute of Biology, Westlake Institute for Advanced Study
    Westlake Laboratory of Life Sciences and Biomedicine)

  • Nicolas A. Larsen

    (Foghorn Therapeutics)

  • Xiaofeng Zhang

    (Westlake University; Institute of Biology, Westlake Institute for Advanced Study
    Westlake Laboratory of Life Sciences and Biomedicine)

  • Yigong Shi

    (Westlake University; Institute of Biology, Westlake Institute for Advanced Study
    Westlake Laboratory of Life Sciences and Biomedicine)

Abstract

Three RNA helicases – DDX42, DDX46 and DHX15 – are found to be associated with human U2 snRNP, but their roles and mechanisms in U2 snRNP and spliceosome assembly are insufficiently understood. Here we report the cryo-electron microscopy (cryo-EM) structures of the DDX42-SF3b complex and a putative assembly precursor of 17S U2 snRNP that contains DDX42 (DDX42-U2 complex). DDX42 is anchored on SF3B1 through N-terminal sequences, with its N-plug occupying the RNA path of SF3B1. The binding mode of DDX42 to SF3B1 is in striking analogy to that of DDX46. In the DDX42-U2 complex, the N-terminus of DDX42 remains anchored on SF3B1, but the helicase domain has been displaced by U2 snRNA and TAT-SF1. Through in vitro assays, we show DDX42 and DDX46 are mutually exclusive in terms of binding to SF3b. Cancer-driving mutations of SF3B1 target the residues in the RNA path that directly interact with DDX42 and DDX46. These findings reveal the distinct roles of DDX42 and DDX46 in assembly of 17S U2 snRNP and provide insights into the mechanisms of SF3B1 cancer mutations.

Suggested Citation

  • Fenghua Yang & Tong Bian & Xiechao Zhan & Zhe Chen & Zhihan Xing & Nicolas A. Larsen & Xiaofeng Zhang & Yigong Shi, 2023. "Mechanisms of the RNA helicases DDX42 and DDX46 in human U2 snRNP assembly," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36489-x
    DOI: 10.1038/s41467-023-36489-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36489-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-36489-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Chengcheng Wang & Zhouyan Guo & Xiechao Zhan & Fenghua Yang & Mingxuan Wu & Xiaofeng Zhang, 2020. "Structure of the yeast Swi/Snf complex in a nucleosome free state," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    2. Zhenwei Zhang & Norbert Rigo & Olexandr Dybkov & Jean-Baptiste Fourmann & Cindy L. Will & Vinay Kumar & Henning Urlaub & Holger Stark & Reinhard Lührmann, 2021. "Structural insights into how Prp5 proofreads the pre-mRNA branch site," Nature, Nature, vol. 596(7871), pages 296-300, August.
    3. Zhenwei Zhang & Cindy L. Will & Karl Bertram & Olexandr Dybkov & Klaus Hartmuth & Dmitry E. Agafonov & Romina Hofele & Henning Urlaub & Berthold Kastner & Reinhard Lührmann & Holger Stark, 2020. "Molecular architecture of the human 17S U2 snRNP," Nature, Nature, vol. 583(7815), pages 310-313, July.
    4. Constantin Cretu & Patricia Gee & Xiang Liu & Anant Agrawal & Tuong-Vi Nguyen & Arun K. Ghosh & Andrew Cook & Melissa Jurica & Nicholas A. Larsen & Vladimir Pena, 2021. "Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Santiago Martínez-Lumbreras & Lena K. Träger & Miriam M. Mulorz & Marco Payr & Varvara Dikaya & Clara Hipp & Julian König & Michael Sattler, 2024. "Intramolecular autoinhibition regulates the selectivity of PRPF40A tandem WW domains for proline-rich motifs," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Lei Shen & Xiaokuang Ma & Yuanyuan Wang & Zhihao Wang & Yi Zhang & Hoang Quoc Hai Pham & Xiaoqun Tao & Yuehua Cui & Jing Wei & Dimitri Lin & Tharindumala Abeywanada & Swanand Hardikar & Levon Halabeli, 2024. "Loss-of-function mutation in PRMT9 causes abnormal synapse development by dysregulation of RNA alternative splicing," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Zachary W. Dwyer & Jeffrey A. Pleiss, 2023. "The problem of selection bias in studies of pre-mRNA splicing," Nature Communications, Nature, vol. 14(1), pages 1-5, December.
    4. Vladislav N. Nikolov & Dhara Malavia & Takashi Kubota, 2022. "SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Yanli Cheng & Zhongtian Shen & Yaqi Gao & Feilong Chen & Huisha Xu & Qinling Mo & Xinlei Chu & Chang-liang Peng & Takese T. McKenzie & Bridgitte E. Palacios & Jian Hu & Hao Zhou & Jiafu Long, 2022. "Phase transition and remodeling complex assembly are important for SS18-SSX oncogenic activity in synovial sarcomas," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36489-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.