IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-42962-4.html
   My bibliography  Save this article

RNA recognition by Npl3p reveals U2 snRNA-binding compatible with a chaperone role during splicing

Author

Listed:
  • Ahmed Moursy

    (Institute of Biochemistry
    Novartis Institutes for BioMedical Research)

  • Antoine Cléry

    (Institute of Biochemistry)

  • Stefan Gerhardy

    (Institute of Biochemistry
    University of Zurich
    Sardona Therapeutics)

  • Katharina M. Betz

    (University of Zurich)

  • Sanjana Rao

    (University of Zurich)

  • Jarosław Mazur

    (University of Zurich)

  • Sébastien Campagne

    (Institute of Biochemistry
    University of Bordeaux)

  • Irene Beusch

    (Institute of Biochemistry
    University of California, San Francisco)

  • Malgorzata M. Duszczyk

    (Institute of Biochemistry)

  • Mark D. Robinson

    (University of Zurich)

  • Vikram Govind Panse

    (University of Zurich
    University of Zurich)

  • Frédéric H.-T. Allain

    (Institute of Biochemistry)

Abstract

The conserved SR-like protein Npl3 promotes splicing of diverse pre-mRNAs. However, the RNA sequence(s) recognized by the RNA Recognition Motifs (RRM1 & RRM2) of Npl3 during the splicing reaction remain elusive. Here, we developed a split-iCRAC approach in yeast to uncover the consensus sequence bound to each RRM. High-resolution NMR structures show that RRM2 recognizes a 5´-GNGG-3´ motif leading to an unusual mille-feuille topology. These structures also reveal how RRM1 preferentially interacts with a CC-dinucleotide upstream of this motif, and how the inter-RRM linker and the region C-terminal to RRM2 contribute to cooperative RNA-binding. Structure-guided functional studies show that Npl3 genetically interacts with U2 snRNP specific factors and we provide evidence that Npl3 melts U2 snRNA stem-loop I, a prerequisite for U2/U6 duplex formation within the catalytic center of the Bact spliceosomal complex. Thus, our findings suggest an unanticipated RNA chaperoning role for Npl3 during spliceosome active site formation.

Suggested Citation

  • Ahmed Moursy & Antoine Cléry & Stefan Gerhardy & Katharina M. Betz & Sanjana Rao & Jarosław Mazur & Sébastien Campagne & Irene Beusch & Malgorzata M. Duszczyk & Mark D. Robinson & Vikram Govind Panse , 2023. "RNA recognition by Npl3p reveals U2 snRNA-binding compatible with a chaperone role during splicing," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42962-4
    DOI: 10.1038/s41467-023-42962-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-42962-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-42962-4?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. Fu-Lung Yeh & Shang-Lin Chang & Golam Rizvee Ahmed & Hsin-I Liu & Luh Tung & Chung-Shu Yeh & Leah Stands Lanier & Corina Maeder & Che-Min Lin & Shu-Chun Tsai & Wan-Yi Hsiao & Wei-Hau Chang & Tien-Hsie, 2021. "Activation of Prp28 ATPase by phosphorylated Npl3 at a critical step of spliceosome remodeling," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    2. Wojciech P. Galej & Max E. Wilkinson & Sebastian M. Fica & Chris Oubridge & Andrew J. Newman & Kiyoshi Nagai, 2016. "Cryo-EM structure of the spliceosome immediately after branching," Nature, Nature, vol. 537(7619), pages 197-201, September.
    3. Gesa Zander & Alexandra Hackmann & Lysann Bender & Daniel Becker & Thomas Lingner & Gabriela Salinas & Heike Krebber, 2016. "mRNA quality control is bypassed for immediate export of stress-responsive transcripts," Nature, Nature, vol. 540(7634), pages 593-596, December.
    4. Daniel Jutzi & Sébastien Campagne & Ralf Schmidt & Stefan Reber & Jonas Mechtersheimer & Foivos Gypas & Christoph Schweingruber & Martino Colombo & Christine Schroetter & Fionna E. Loughlin & Anny Dev, 2020. "Aberrant interaction of FUS with the U1 snRNA provides a molecular mechanism of FUS induced amyotrophic lateral sclerosis," Nature Communications, Nature, vol. 11(1), pages 1-14, 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. Sébastien Campagne & Daniel Jutzi & Florian Malard & Maja Matoga & Ksenija Romane & Miki Feldmuller & Martino Colombo & Marc-David Ruepp & Frédéric H-T. Allain, 2023. "Molecular basis of RNA-binding and autoregulation by the cancer-associated splicing factor RBM39," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Bangjun Zhou & Huihui Yu & Yong Xue & Mu Li & Chi Zhang & Bin Yu, 2024. "The spliceosome-associated protein CWC15 promotes miRNA biogenesis in Arabidopsis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Jana Aupič & Jure Borišek & Sebastian M. Fica & Wojciech P. Galej & Alessandra Magistrato, 2023. "Monovalent metal ion binding promotes the first transesterification reaction in the spliceosome," Nature Communications, Nature, vol. 14(1), pages 1-10, 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_s41467-023-42962-4. 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.