RNA-Binding Proteins: Splicing Factors and Disease

Biomolecules. 2015 May 13;5(2):893-909. doi: 10.3390/biom5020893.


Pre-mRNA splicing is mediated by interactions of the Core Spliceosome and an array of accessory RNA binding proteins with cis-sequence elements. Splicing is a major regulatory component in higher eukaryotes. Disruptions in splicing are a major contributor to human disease. One in three hereditary disease alleles are believed to cause aberrant splicing. Hereditary disease alleles can alter splicing by disrupting a splicing element, creating a toxic RNA, or affecting splicing factors. One of the challenges of medical genetics is identifying causal variants from the thousands of possibilities discovered in a clinical sequencing experiment. Here we review the basic biochemistry of splicing, the mechanisms of splicing mutations, the methods for identifying splicing mutants, and the potential of therapeutic interventions.

Keywords: RNA-binding proteins; motif; splicing.

Publication types

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

MeSH terms

  • Animals
  • Genetic Diseases, Inborn / genetics*
  • Humans
  • Polymorphism, Single Nucleotide
  • RNA Splicing*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Spliceosomes / metabolism


  • RNA-Binding Proteins