Plasmodium falciparumvar Gene Is Activated by Its Antisense Long Noncoding RNA

Abstract

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