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  1. Article

    Open Access

    Monovalent metal ion binding promotes the first transesterification reaction in the spliceosome

    Cleavage and formation of phosphodiester bonds in nucleic acids is accomplished by large cellular machineries composed of both protein and RNA. Long thought to rely on a two-metal-ion mechanism for catalysis, ...

    Jana Aupič, Jure Borišek, Sebastian M. Fica, Wojciech P. Galej… in Nature Communications (2023)

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  2. Article

    Open Access

    psiCLIP reveals dynamic RNA binding by DEAH-box helicases before and after exon ligation

    RNA helicases remodel the spliceosome to enable pre-mRNA splicing, but their binding and mechanism of action remain poorly understood. To define helicase-RNA contacts in specific spliceosomal states, we develo...

    Lisa M. Strittmatter, Charlotte Capitanchik, Andrew J. Newman… in Nature Communications (2021)

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  3. No Access

    Article

    Cryo-electron microscopy snapshots of the spliceosome: structural insights into a dynamic ribonucleoprotein machine

    The spliceosome excises introns from pre-messenger RNAs using an RNA-based active site that is cradled by a dynamic protein scaffold. A recent revolution in cryo-electron microscopy (cryo-EM) has led to near-a...

    Sebastian M Fica, Kiyoshi Nagai in Nature Structural & Molecular Biology (2017)

  4. No Access

    Article

    Structure of a spliceosome remodelled for exon ligation

    The cryo-electron microscopy structure of a yeast spliceosome stalled before mature RNA formation provides insight into the mechanism of exon ligation.

    Sebastian M. Fica, Chris Oubridge, Wojciech P. Galej, Max E. Wilkinson… in Nature (2017)

  5. No Access

    Article

    Cryo-EM structure of the spliceosome immediately after branching

    Precursor mRNA (pre-mRNA) splicing proceeds by two consecutive transesterification reactions via a lariat–intron intermediate. Here we present the 3.8 Å cryo-electron microscopy structure of the spliceosome im...

    Wojciech P. Galej, Max E. Wilkinson, Sebastian M. Fica, Chris Oubridge… in Nature (2016)

  6. No Access

    Article

    Evidence for a group II intron–like catalytic triplex in the spliceosome

    It has long been thought that the catalytic RNAs of self-splicing group II introns and the spliceosome function by similar mechanisms. Now, a combination of genetic, cross-linking, and biochemical analyses of ...

    Sebastian M Fica, Melissa A Mefford… in Nature Structural & Molecular Biology (2014)

  7. No Access

    Article

    RNA catalyses nuclear pre-mRNA splicing

    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-sp...

    Sebastian M. Fica, Nicole Tuttle, Thaddeus Novak, Nan-Sheng Li, Jun Lu… in Nature (2013)