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The SMN complex drives structural changes in human snRNAs to enable snRNP assembly

Author

Listed:
  • Josef Pánek

    (Institute of Microbiology, Czech Academy of Sciences)

  • Adriana Roithová

    (Czech Academy of Sciences
    Czech Academy of Sciences)

  • Nenad Radivojević

    (Czech Academy of Sciences)

  • Michal Sýkora

    (Czech Academy of Sciences)

  • Archana Bairavasundaram Prusty

    (University of Würzburg)

  • Nicholas Huston

    (Yale University)

  • Han Wan

    (Yale University)

  • Anna Marie Pyle

    (Yale University
    Yale University
    Howard Hughes Medical Institute)

  • Utz Fischer

    (University of Würzburg)

  • David Staněk

    (Czech Academy of Sciences)

Abstract

Spliceosomal snRNPs are multicomponent particles that undergo a complex maturation pathway. Human Sm-class snRNAs are generated as 3′-end extended precursors, which are exported to the cytoplasm and assembled together with Sm proteins into core RNPs by the SMN complex. Here, we provide evidence that these pre-snRNA substrates contain compact, evolutionarily conserved secondary structures that overlap with the Sm binding site. These structural motifs in pre-snRNAs are predicted to interfere with Sm core assembly. We model structural rearrangements that lead to an open pre-snRNA conformation compatible with Sm protein interaction. The predicted rearrangement pathway is conserved in Metazoa and requires an external factor that initiates snRNA remodeling. We show that the essential helicase Gemin3, which is a component of the SMN complex, is crucial for snRNA structural rearrangements during snRNP maturation. The SMN complex thus facilitates ATP-driven structural changes in snRNAs that expose the Sm site and enable Sm protein binding.

Suggested Citation

  • Josef Pánek & Adriana Roithová & Nenad Radivojević & Michal Sýkora & Archana Bairavasundaram Prusty & Nicholas Huston & Han Wan & Anna Marie Pyle & Utz Fischer & David Staněk, 2023. "The SMN complex drives structural changes in human snRNAs to enable snRNP assembly," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42324-0
    DOI: 10.1038/s41467-023-42324-0
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    References listed on IDEAS

    as
    1. Clemens Plaschka & Pei-Chun Lin & Kiyoshi Nagai, 2017. "Structure of a pre-catalytic spliceosome," Nature, Nature, vol. 546(7660), pages 617-621, June.
    2. Holger Stark & Prakash Dube & Reinhard Lührmann & Berthold Kastner, 2001. "Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle," Nature, Nature, vol. 409(6819), pages 539-542, January.
    3. Karl Bertram & Dmitry E. Agafonov & Wen-Ti Liu & Olexandr Dybkov & Cindy L. Will & Klaus Hartmuth & Henning Urlaub & Berthold Kastner & Holger Stark & Reinhard Lührmann, 2017. "Cryo-EM structure of a human spliceosome activated for step 2 of splicing," Nature, Nature, vol. 542(7641), pages 318-323, February.
    4. Adelaine K. W. Leung & Kiyoshi Nagai & Jade Li, 2011. "Structure of the spliceosomal U4 snRNP core domain and its implication for snRNP biogenesis," Nature, Nature, vol. 473(7348), pages 536-539, May.
    5. Daniel A. Pomeranz Krummel & Chris Oubridge & Adelaine K. W. Leung & Jade Li & Kiyoshi Nagai, 2009. "Crystal structure of human spliceosomal U1 snRNP at 5.5 Å resolution," Nature, Nature, vol. 458(7237), pages 475-480, March.
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