Splicing role of PRPF40A/B paralogs in human myeloid cells

• Main Author: Tan, Cheryl Weiqi
• Other Authors: Francesc Xavier Roca Castella
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2022
• Subjects: Science::Biological sciences::Molecular biology
• Online Access: https://hdl.handle.net/10356/155738
• Institution: Nanyang Technological University

PRPF40A and PRPF40B are the human orthologs of the essential yeast splicing factor Prp40, however their splicing role is not clearly understood. The expression of PRPF40A and PRPF40B is high and low respectively in acute myeloid leukemia (AML) as compared to solid tumors. This study explored the splicing role of PRPF40A/B paralogs in AML cell maintenance, myeloid cell differentiation and immune response. Upon PRPF40A knockdown, HL-60 cells displayed increased cell death, decreased proliferation and slight differentiation phenotype with upregulation of immune activation genes. Interestingly, cell death but not proliferation was rescued with PRPF40B overexpression. Transcriptomic analysis of PRPF40A knockdown cells revealed that 80% of cassette exons were downregulated, implying its role as a splicing activator. Overall, PRPF40A and PRPF40B showed largely differing function and targets with potential implications for AML.