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Plasmodium falciparum  erythrocyte membrane protein 1, encoded by  var  gene, is an immunodominant antigen mediating immune evasion in humans. At a given time, only a single  var  gene is commonly expressed in one parasite. However, the regulation mechanism of  var  transcription remains largely unknown. In this study, we identified the antisense long non-coding RNA (aslncRNA) derived from  var  intron as an activation factor for the corresponding  var  gene. The exogenous artificial  var  aslncRNA transcribed by T7 RNA polymerase from episome can specifically activate the homologous  var  gene, and the exogenous aslncRNA activates transcription of both  var  mRNA and endogenous aslncRNA in a manner independent of the conserved intron sequence within the  var  gene family. Interestingly, the newly activated  var  gene and the previously dominant  var  gene then could be co-expressed in the same parasite nuclei, which suggests that the aslncRNA-mediated  var  gene activation could escape from the control of mutually exclusively expression of the  var  gene family. Together, our work shows that  var  aslncRNA is the activator responsible for  var  gene transcriptional regulation.

Plasmodium falciparumvar Gene Is Activated by Its Antisense Long Noncoding RNA