KNOCKDOWN OF SPLICING COMPLEX PROTEIN PCBP2 REDUCES EXTRAVILLOUS TROPHOBLAST DIFFERENTIATION THROUGH TRANSCRIPT SWITCHING

Mutations in the LINC-HELLP non-coding RNA (HELLPAR), and associated with familial forms of the pregnancy-specific HELLP syndrome, negatively affect extravillous trophoblast (EVT) differentiation and disturb the binding of RNA splicing complex protein PCBP2 to LINC-HELLP. In this study, we show that knockdown of PCBP2 in the HTR8/SVneo EVT cell line and in human first trimester placental explants leads to reduced differentiation of EVTs. Additionally, PCBP2 silencing in HTR8/SVneo cells leads to a switch in splicing for a large number of genes with predominant functions in cell morphology, cellular assembly and organization, and cellular function and maintenance,as identified by RNA-Seq. EVTs, upon differentiation, alter their morphology, cellular assembly and their capacity to properly invade the decidua of the mother. PCBP2 appears to be a paramount regulator of these differentiation mechanisms, where its disturbed binding to LINC-HELLP could contribute to dysfunctional placental development as seen in the HELLP syndrome.