The Role Of Intron Retention In Cancer

Intron retention (IR) occurs when the splicing machinery fails to excise introns from primarytranscripts. We have shown that IR is a widespread mechanism of post-transcriptional generegulation and can induce diverse downstream effects. We also found evidence that IR affectsfunctionally related genes in granulocytes throughout evolution. Retained introns have similarcharacteristics and there is a strong anti-correlation between the number of intron-retaining genesand the number of protein-coding genes in a genome. IR was recently described as mechanism oftumor-suppressor inactivation, which suggests a significant contribution to cancer emergence andprogression. An analysis of TCGA RNA-seq data revealed that acute myeloid leukaemia has thehighest number of intron retaining transcripts among 16 cancers analyned. Compelling evidenceindicates that there is increased perturbation in the way genes function in leukaemia due to IRinducedregulation. Currently, we utiline a computational approach to analyne vast amounts ofbiomedical data that will enhance our understanding of IR. Our preliminary results suggest that IRis an independent mechanism of post-transcriptional gene regulation that supplements or evencooperates with other forms gene regulation and relates to causes for the emergence andprogression of different cancers including leukaemia.