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RNA catalyses nuclear pre-mRNA splicing

Author

Listed:
  • Sebastian M. Fica

    (Graduate Program in Cell and Molecular Biology, The University of Chicago
    Cummings Life Sciences Center, 920 East 58th Street, The University of Chicago)

  • Nicole Tuttle

    (929 East 57th Street, The University of Chicago)

  • Thaddeus Novak

    (Gordon Center for Integrative Science, 929 East 57th Street, The University of Chicago)

  • Nan-Sheng Li

    (Gordon Center for Integrative Science, 929 East 57th Street, The University of Chicago)

  • Jun Lu

    (929 East 57th Street, The University of Chicago)

  • Prakash Koodathingal

    (Cummings Life Sciences Center, 920 East 58th Street, The University of Chicago)

  • Qing Dai

    (929 East 57th Street, The University of Chicago)

  • Jonathan P. Staley

    (Cummings Life Sciences Center, 920 East 58th Street, The University of Chicago)

  • Joseph A. Piccirilli

    (929 East 57th Street, The University of Chicago
    Gordon Center for Integrative Science, 929 East 57th Street, The University of Chicago)

Abstract

In nuclear pre-messenger RNA splicing, introns are excised by the spliceosome, a dynamic machine composed of both proteins and small nuclear RNAs (snRNAs). Over thirty years ago, after the discovery of self-splicing group II intron RNAs, the snRNAs were proposed to catalyse splicing. However, no definitive evidence for a role of either RNA or protein in catalysis by the spliceosome has been reported so far. By using metal rescue strategies in spliceosomes from budding yeast, here we show that the U6 snRNA catalyses both of the two splicing reactions by positioning divalent metals that stabilize the leaving groups during each reaction. Notably, all of the U6 catalytic metal ligands we identified correspond to the ligands observed to position catalytic, divalent metals in crystal structures of a group II intron RNA. These findings indicate that group II introns and the spliceosome share common catalytic mechanisms and probably common evolutionary origins. Our results demonstrate that RNA mediates catalysis within the spliceosome.

Suggested Citation

  • Sebastian M. Fica & Nicole Tuttle & Thaddeus Novak & Nan-Sheng Li & Jun Lu & Prakash Koodathingal & Qing Dai & Jonathan P. Staley & Joseph A. Piccirilli, 2013. "RNA catalyses nuclear pre-mRNA splicing," Nature, Nature, vol. 503(7475), pages 229-234, November.
    • Handle: RePEc:nat:nature:v:503:y:2013:i:7475:d:10.1038_nature12734
    DOI: 10.1038/nature12734
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    Cited by:

    1. 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.
    2. Seisuke Yamashita & Kozo Tomita, 2023. "Mechanism of U6 snRNA oligouridylation by human TUT1," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    3. Xiechao Zhan & Yichen Lu & Yigong Shi, 2024. "Molecular basis for the activation of human spliceosome," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

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