Alternative splicing of RNA is a fundamental biological process that affects almost all multi-exonic genes to promote protein diversity. Of the 3 modes of RNA splicing that also include exon skipping and alternative splice site usage, intron retention (IR) is the least abundant and least understood. Despite isolated instances of IR-associated biological function, IR has been widely regarded as a failure in the splicing machinery to excise intronic sequences from pre-messenger RNAs. Since an overall role for IR is unknown, we systematically examined the impact of IR in normal primary myeloid cells during differentiation. Using messenger RNA sequencing (mRNA-seq) and a novel algorithm we termed IRFinder, we determined intron-retaining genes that were differentially regulated in FACS-purified cells at three progressive stages of mouse granulopoiesis; CD34+Kit+Gr-1low promyelocytes, CD34−Kit−Gr-1mid myelocytes and CD34−Kit−Gr-1high granulocytes. We demonstrated that IR exhibits a specific pattern of dynamic regulation in 86 genes during granulocytic differentiation.
Rasko:Genea Ltd: Employment; Rarecyte: Consultancy.
Asterisk with author names denotes non-ASH members.