RNA mis-splicing in disease

Nat Rev Genet. 2016 Jan;17(1):19-32. doi: 10.1038/nrg.2015.3. Epub 2015 Nov 23.


The human transcriptome is composed of a vast RNA population that undergoes further diversification by splicing. Detecting specific splice sites in this large sequence pool is the responsibility of the major and minor spliceosomes in collaboration with numerous splicing factors. This complexity makes splicing susceptible to sequence polymorphisms and deleterious mutations. Indeed, RNA mis-splicing underlies a growing number of human diseases with substantial societal consequences. Here, we provide an overview of RNA splicing mechanisms followed by a discussion of disease-associated errors, with an emphasis on recently described mutations that have provided new insights into splicing regulation. We also discuss emerging strategies for splicing-modulating therapy.

Publication types

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

MeSH terms

  • Alternative Splicing*
  • Animals
  • Base Sequence
  • Genetic Therapy
  • Humans
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / metabolism
  • Muscular Dystrophy, Duchenne / therapy
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Spliceosomes / physiology


  • Protein Isoforms
  • RNA, Messenger