Alternative Splicing: Role of Pseudoexons in Human Genetic Disease


In the pre‐mRNA splicing field the term ‘pseudoexons’ has been introduced to describe all those sequences usually localised deep in intronic regions that resemble real exons in appearance but are ignored by the spliceosomal machinery. Although we now know that some of these sequences are important for regulatory purposes it is also true that aberrant pseudoexon activation is increasingly described as one of the major causes of human disease. Several recent studies on pseudoexon inclusion–exclusion mechanisms have allowed researchers to gain further insight with regards to the mechanism that the spliceosome uses to discriminate between true and false exons during the normal splicing process. Most importantly, the newly gained knowledge regarding pseudoexon biology has been extensively exploited to devise novel therapeutic strategies aimed at inhibiting their inclusion in human patients.

Key Concepts:

  • Pseudoexons (also known as ‘false exons’) are very abundant in all eukaryotic genes, especially those harbouring long intronic sequences.

  • In normal conditions, pseudoexon inclusion in mature mRNAs is efficiently inhibited.

  • Mutational events that activate aberrant pseudoexon inclusion are a common source of disease‐causing mutations in humans.

  • A variety of novel therapeutic approaches principally based on antisense oligonucleotide (AON) technology is currently being developed to inhibit their inclusion in human patients.

Keywords: pseudoexons; exons; introns; pre‐mRNA splicing; genetic disease; gene therapy

Figure 1.

Schematic representation of the basic pre‐mRNA splicing process.

Figure 2.

Possible origins and consequences of aberrant pseudoexon insertion in the normal splicing process.

Figure 3.

Use of AON technology to inhibit pseudoexon inclusion in the mature mRNA molecule.



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Further Reading

Buratti E, Baralle M and Baralle FE (2006) Defective splicing, disease and therapy: searching for master checkpoints in exon definition. Nucleic Acids Research 34: 3494–3510.

Stamm S, Ben‐Ari S, Rafalska I et al. (2005) Function of alternative splicing. Gene 344: 1–20.

Stamm S, Smith CW and Lurhmann R (eds) (2011) Alternative pre‐mRNA Splicing: Theory and Protocols. Weinheim: Wiley‐VCH.

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How to Cite close
Emanuele, Buratti(Sep 2011) Alternative Splicing: Role of Pseudoexons in Human Genetic Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0023579]