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Pre-mRNA Splicing and the Spliceosome: Assembly, Catalysis, and Fidelity

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Fungal RNA Biology

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Abstract

At the level of gene architecture, the widespread presence of interrupting sequences in eukaryotic genes serves as a defining difference between eukaryotic organisms and other domains of life. These interrupting sequences, known as introns, must be precisely removed from pre-messenger RNA (pre-mRNA) transcripts. Concomitantly, the coding regions, or exons, are joined together through a nuclear-localized process known as pre-mRNA splicing. A number of splicing factors, both protein and RNA, assemble into a multimegadalton splicing machine known as the spliceosome, which is responsible for identifying the intronic regions and positioning the pre-mRNA substrate in a favorable orientation for the splicing reactions to occur. While the chemical steps of splicing—two sequential transesterification reactions—are identical in all eukaryotes, the gene architecture and splicing apparatus can differ substantially. Here, we review our current understanding of the splicing process with an emphasis on the model organism Saccharomyces cerevisiae. We discuss the key features of introns, along with mechanistic aspects of the splicing cycle, namely spliceosome assembly, catalysis, and spliceosome disassembly. We also highlight recent discoveries supporting the role of kinetic proofreading in ensuring the fidelity of splicing.

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Acknowledgments

This work was supported by NSERC Discovery Grant 298521 to SDR and an NSERC PGS award to EAD, as well as by awards from UNBC’s Office of Research.

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Authors and Affiliations

  1. Department of Chemistry, University of Northern British Columbia, Prince George, BC, Canada

    Stephen D. Rader

  2. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada

    Elizabeth A. Dunn

Authors
  1. Elizabeth A. Dunn
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  2. Stephen D. Rader
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Correspondence to Stephen D. Rader .

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Editors and Affiliations

  1. Centre for Plant Biotechnology and Genom, Universidad Politécnica de Madrid, Pozuelo de Alarcón (Madrid), Spain

    Ane Sesma

  2. Kent Fungal Group School of Biosciences, University of Kent, Kent, United Kingdom

    Tobias von der Haar

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Dunn, E.A., Rader, S.D. (2014). Pre-mRNA Splicing and the Spliceosome: Assembly, Catalysis, and Fidelity. In: Sesma, A., von der Haar, T. (eds) Fungal RNA Biology. Springer, Cham. https://doi.org/10.1007/978-3-319-05687-6_2

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