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The RNA Exosome and Human Disease

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The Eukaryotic RNA Exosome

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2062))

Abstract

The evolutionarily conserved RNA exosome is a multisubunit ribonuclease complex that processes and/or degrades numerous RNAs. Recently, mutations in genes encoding both structural and catalytic subunits of the RNA exosome have been linked to human disease. Mutations in the structural exosome gene EXOSC2 cause a distinct syndrome that includes retinitis pigmentosa, hearing loss, and mild intellectual disability. In contrast, mutations in the structural exosome genes EXOSC3 and EXOSC8 cause pontocerebellar hypoplasia type 1b (PCH1b) and type 1c (PCH1c), respectively, which are related autosomal recessive, neurodegenerative diseases. In addition, mutations in the structural exosome gene EXOSC9 cause a PCH-like disease with cerebellar atrophy and spinal motor neuronopathy. Finally, mutations in the catalytic exosome gene DIS3 have been linked to multiple myeloma, a neoplasm of plasma B cells. How mutations in these RNA exosome genes lead to distinct, tissue-specific diseases is not currently well understood. In this chapter, we examine the role of the RNA exosome complex in human disease and discuss the mechanisms by which mutations in different exosome subunit genes could impair RNA exosome function and give rise to diverse diseases.

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Change history

  • 01 December 2020

    A correction has been published.

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Acknowledgments

We thank our colleagues Elena Conti, Christopher D. Lima, and Ambro van Hoof for sharing their expertise in analysis of the RNA exosome as well as members of the Corbett lab for helpful discussions and comments. This work was supported by both an NIH R01 grant (GM058728) and NIH R21 grant (AG054206) to AHC and both an NIH F32 grant (GM125350) and a Postdoctoral Enrichment Award from the Burroughs Wellcome Fund to DJM.

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Authors and Affiliations

  1. Department of Biology, RRC 1021, Emory University, Atlanta, GA, USA

    Milo B. Fasken, Derrick J. Morton, Stephanie K. Jones, Sara W. Leung & Anita H. Corbett

  2. Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA

    Emily G. Kuiper

  3. Genetics and Molecular Biology Graduate Program, Emory University, Atlanta, GA, USA

    Stephanie K. Jones

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  1. Milo B. Fasken
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  2. Derrick J. Morton
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  3. Emily G. Kuiper
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  4. Stephanie K. Jones
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  5. Sara W. Leung
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  6. Anita H. Corbett
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Correspondence to Milo B. Fasken or Anita H. Corbett .

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Editors and Affiliations

  1. Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY, USA

    John LaCava

  2. Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic

    Štěpánka Vaňáčová

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Fasken, M.B., Morton, D.J., Kuiper, E.G., Jones, S.K., Leung, S.W., Corbett, A.H. (2020). The RNA Exosome and Human Disease. In: LaCava, J., Vaňáčová, Š. (eds) The Eukaryotic RNA Exosome. Methods in Molecular Biology, vol 2062. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9822-7_1

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  • DOI: https://doi.org/10.1007/978-1-4939-9822-7_1

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