An axonemal intron splicing program sustainsPlasmodiummale development

Abstract

AbstractDifferentiation of male gametocyte into flagellated fertile male gamete relies on the axoneme assembly, a major component of male development for mosquito transmission of malaria parasite. RNA-binding protein (RBP)-mediated post-transcription regulation plays important roles in eukaryotic sexual development, including thePlasmodiumfemale development. However, the role of RBP in defining thePlasmodiummale transcriptome and its function in the male gametogenesis remain elusive. Here, we screened the gender expression of the genome-wide RBPs and identified an undescribed male-specific RBP geneRbpm1in thePlasmodium. RBPm1 is localized in the nucleus of male gametocytes. RBPm1-deficient parasites fail to assemble the axoneme for male gametogenesis and thus mosquito transmission. RBPm1 interacts with spliceosome E complex and regulates splicing initiation of certain introns in a group of 26 axonemal genes. RBPm1 deficiency results in intron retention and protein loss of these axonemal genes. Intron deletion restores axonemal proteins expression and partially rectifies axonemal defects in RBPm1-null gametocytes. Further splicing assays in both reporter and endogenous genes exhibit stringent recognition of the axonemal introns by RBPm1. Therefore, the splicing activator RBPm1 and its target introns constitute an axonemal intron splicing program in the post-transcription regulation essential forPlasmodiummale development.