ChIRP-seq reveals the GC-rich ncRNA is required for monoallelic activation of virulence genes in Plasmodium falciparum

Singular expression of members of gene families determine phenotypic outcomes at the single cell level in a wide variety of organisms. The human malaria parasite Plasmodium falciparum uses monoallelic expression of variant surface adhesion molecules encoded by the 60-member var gene family as a host immune evasion mechanism. Although progress has been made in the molecular understanding of the default silencing mechanism, the singular gene activation process of an expressed var member remains elusive. In this study, we show that a polymerase III transcribed clonally variant gene family that codes for 15 GC-rich ncRNAs regulates var activation. We identify the physical interaction between the transcribed ncRNA and the active var gene loci by Chromatin Isolation by RNA Purification (ChIRP-seq). Our work suggests an enhancer-like function of ncRNA for singular var gene expression.