Alternative Splicing May Not Be the Key to Proteome Complexity

Trends Biochem Sci. 2017 Feb;42(2):98-110. doi: 10.1016/j.tibs.2016.08.008. Epub 2016 Oct 3.


Alternative splicing is commonly believed to be a major source of cellular protein diversity. However, although many thousands of alternatively spliced transcripts are routinely detected in RNA-seq studies, reliable large-scale mass spectrometry-based proteomics analyses identify only a small fraction of annotated alternative isoforms. The clearest finding from proteomics experiments is that most human genes have a single main protein isoform, while those alternative isoforms that are identified tend to be the most biologically plausible: those with the most cross-species conservation and those that do not compromise functional domains. Indeed, most alternative exons do not seem to be under selective pressure, suggesting that a large majority of predicted alternative transcripts may not even be translated into proteins.

Keywords: RNA-seq; alternative splicing; dominant isoforms; functional isoforms; homology; proteomics.

Publication types

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

MeSH terms

  • Alternative Splicing / genetics*
  • Exons
  • Protein Isoforms / genetics
  • Proteome / genetics*
  • Proteomics


  • Protein Isoforms
  • Proteome