[Deregulation of pre-messenger RNA splicing and rare diseases]

Med Sci (Paris). 2016 Dec;32(12):1111-1119. doi: 10.1051/medsci/20163212015. Epub 2017 Jan 3.
[Article in French]


Most of protein-coding human genes are subjected to alternative pre-mRNA splicing. This mechanism is highly regulated to precisely modulate detection of specific splice sites. This regulation is under control of the spliceosome and several splicing factors are also required to modulate the alternative usage of splice sites. Splicing factors and spliceosome components recognize splicing signals and regulatory sequences of the pre-mRNAs. These splicing sequences make splicing susceptible to polymorphisms and mutations. Examples of associations between human rare diseases and defects in pre-messenger RNA splicing are accumulating. Although many alterations are caused by mutations in splicing sequence (i.e., cis acting mutations), recent studies described the disruptive impact of mutations within spliceosome components or splicing factors (i.e., trans acting mutations). Following growing of knowledge regarding splicing regulation, several approaches have been developed to compensate for the effect of deleterious mutations and to restore sufficient amounts of functional protein.

Publication types

  • Review

MeSH terms

  • Alternative Splicing
  • Humans
  • Mutation / physiology
  • RNA Precursors / metabolism*
  • RNA Splicing / physiology*
  • Rare Diseases / genetics*


  • RNA Precursors