Characterisation of splicing regulation by PRPF40A/B paralogues

Alternative splicing plays an essential role in various physiological processes such as cellular differentiation and development. A tight regulation of alternative splicing is critical for the maintenance of normal physiological processes and splicing dysregulation has been found to be implicated in various diseases. As splicing factors play important roles in the regulation of alternative splicing, this project seeks to understand the functional differences and similarities between the splicing factor paralogues PRPF40A and PRPF40B in human promyelocytic leukaemia (HL-60) cells. Preliminary data has shown PRPF40A to be critical for HL-60 cell survival as PRPF40A knockdown led to significant levels of cell death, which could be rescued by PRPF40B overexpression. In this study, transcriptomic analysis revealed that PRPF40A and PRPF40B regulate exons with differing properties. While PRPF40A regulates exons flanked by short high GC content introns, PRPF40B regulates exons flanked by introns of lower GC content. Additionally, the region of highest divergence between both paralogues does not seem to play a role in functionally differentiating PRPF40A and PRPF40B. Overall, both paralogues do not fully overlap in their splicing regulatory function, and this may potentially be implicated in myeloid cell physiology.Bachelor of Science in Biological Science