The RNA Exosome and Human Disease

  • Milo B. FaskenEmail author
  • Derrick J. Morton
  • Emily G. Kuiper
  • Stephanie K. Jones
  • Sara W. Leung
  • Anita H. CorbettEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 2062)


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.

Key words

Pontocerebellar hypoplasia Retinitis pigmentosa Spinal motor neuronopathy Multiple myeloma RNA exosome EXOSC2 EXOSC3 EXOSC8 EXOSC9 DIS3 Rrp4 Rrp40 Rrp43 Rrp45 Rrp44 



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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Milo B. Fasken
    • 1
    Email author
  • Derrick J. Morton
    • 1
  • Emily G. Kuiper
    • 2
  • Stephanie K. Jones
    • 1
    • 3
  • Sara W. Leung
    • 1
  • Anita H. Corbett
    • 1
    Email author
  1. 1.Department of Biology, RRC 1021Emory UniversityAtlantaUSA
  2. 2.Department of Cancer Immunology and VirologyDana-Farber Cancer InstituteBostonUSA
  3. 3.Genetics and Molecular Biology Graduate ProgramEmory UniversityAtlantaUSA

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