Analysis of alternative splicing profiles and the role of RBM47 in myeloid maturation

Abstract

Myeloid leukocytes, such as neutrophils and monocytes, are critical for innate immunity. As splicing defects are common in malignancies that disrupt myeloid maturation, we hypothesise that alternative splicing (AS) programmes are important in regulating myelopoiesis. To study AS during human neutrophil differentiation, HL-60 myeloid leukaemia cells were used as a model, where an increase in differential cassette exon events associated with non-productive mRNA isoforms was observed. Additionally, being primarily expressed in the neutrophilic and monocytic lineages among leukocytes, the role of the splicing factor RBM47 in myelopoiesis was examined, with HL-60 cells overexpressing RBM47 exhibiting enhancements in vitamin D3-induced monocytic differentiation and hundreds of AS changes. Furthermore, the re-analysis of human myeloid cell RNA-seq datasets revealed that exons neighbouring high GC-content introns were preferentially upregulated or downregulated in several datasets. Overall, several AS trends associated with myeloid maturation was examined, along with the putative myelopoietic regulatory role of RBM47.