Role of pseudoexons and pseudointrons in human cancer

In all eukaryotic organisms, pre-mRNA splicing and alternative splicing processes play an essential role in regulating the flow of information required to drive complex developmental and metabolic pathways. As a result, eukaryotic cells have developed a very efficient macromolecular machinery, called the spliceosome, to correctly recognize the pre-mRNA sequences that need to be inserted in a mature mRNA (exons) from those that should be removed (introns). In healthy individuals, alternative and constitutive splicing processes function with a high degree of precision and fidelity in order to ensure the correct working of this machinery. In recent years, however, medical research has shown that alterations at the splicing level play an increasingly important role in many human hereditary diseases, neurodegenerative processes, and especially in cancer origin and progression. In this minireview, we will focus on several genes whose association with cancer has been well established in previous studies, such as ATM, BRCA1/A2, and NF1. In particular, our objective will be to provide an overview of the known mechanisms underlying activation/repression of pseudoexons and pseudointrons; the possible utilization of these events as biomarkers of tumor staging/grading; and finally, the treatment options for reversing pathologic splicing events.