Plasmodium falciparum PfRUVBL proteins bind at the TARE region and var gene promoter located in the subtelomeric region

Pathog Dis. 2022 Jul 21;80(1):ftac018. doi: 10.1093/femspd/ftac018.

Abstract

In order to survive and establish infection, the Plasmodium parasite employs various strategies to evade the host immune response. The var genes family, a repertoire of 60 genes, expresses parasite-specific protein PfEMP1, a variable surface antigen, on the membrane of infected erythrocytes, and by continuously switching the variants of PfEMP1, help the parasite to avoid detection and destruction by the host immune system during the intra-erythrocytic developmental cycle. Although chromatin modifications are recognised to be a prominent phenomenon in regulation of mono-allelic expression of these var genes, the precise histone codes and molecular players and mechanisms guiding these modifications have yet to be unravelled in depth. In this study, we have functionally characterised RUVBL proteins of Plasmodium falciparum and shown that PfMYST (an essential lysine acetyl transferase) and PfRUVBL protein complex occupy the TARE region and var gene promoter in the ring stage of the parasite. Further, we have demonstrated that the PfMYST/PfRUVBL complex interacts with core histones, H3 and H4. Overall the findings of this study add further information by identifying the potential role of epigenetic regulators, PfMYST and PfRUVBL, in the regulation of monoallelic expression of var genes in the malaria parasite.

Keywords: Plasmodium; var gene; HAT; PfMYST; PfRUVBL; chromatin modification; immune evasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Erythrocytes
  • Histones / genetics
  • Histones / metabolism
  • Plasmodium falciparum* / genetics
  • Plasmodium falciparum* / metabolism
  • Protozoan Proteins* / genetics
  • Protozoan Proteins* / metabolism

Substances

  • Histones
  • Protozoan Proteins