The RNA Exosome and Human Disease

Methods Mol Biol. 2020;2062:3-33. doi: 10.1007/978-1-4939-9822-7_1.


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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease / genetics*
  • Exosomes / genetics*
  • Humans
  • Mutation / genetics
  • RNA / genetics*


  • RNA