Context-dependent control of alternative splicing by RNA-binding proteins

Nat Rev Genet. 2014 Oct;15(10):689-701. doi: 10.1038/nrg3778. Epub 2014 Aug 12.


Sequence-specific RNA-binding proteins (RBPs) bind to pre-mRNA to control alternative splicing, but it is not yet possible to read the 'splicing code' that dictates splicing regulation on the basis of genome sequence. Each alternative splicing event is controlled by multiple RBPs, the combined action of which creates a distribution of alternatively spliced products in a given cell type. As each cell type expresses a distinct array of RBPs, the interpretation of regulatory information on a given RNA target is exceedingly dependent on the cell type. RBPs also control each other's functions at many levels, including by mutual modulation of their binding activities on specific regulatory RNA elements. In this Review, we describe some of the emerging rules that govern the highly context-dependent and combinatorial nature of alternative splicing regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alternative Splicing*
  • Animals
  • Binding Sites / genetics
  • Cellular Microenvironment / genetics
  • Humans
  • Organ Specificity / genetics
  • Protein Binding
  • RNA-Binding Proteins / physiology*
  • Regulatory Elements, Transcriptional / physiology*


  • RNA-Binding Proteins