title: Putative DNA G-quadruplex formation within the promoters of Plasmodium falciparum var genes.
abstract: BACKGROUND
  Guanine-rich nucleic acid sequences are capable of folding into an intramolecular four-stranded structure called a G-quadruplex. When found in gene promoter regions, G-quadruplexes can downregulate gene expression, possibly by blocking the transcriptional machinery. Here we have used a genome-wide bioinformatic approach to identify Putative G-Quadruplex Sequences (PQS) in the Plasmodium falciparum genome, along with biophysical techniques to examine the physiological stability of P. falciparum PQS in vitro.
  
  
  RESULTS
  We identified 63 PQS in the non-telomeric regions of the P. falciparum clone 3D7. Interestingly, 16 of these PQS occurred in the upstream region of a subset of the P. falciparum var genes (group B var genes). The var gene family encodes PfEMP1, the parasite's major variant antigen and adhesin expressed at the surface of infected erythrocytes, that plays a key role in malaria pathogenesis and immune evasion. The ability of the PQS found in the upstream regions of group B var genes (UpsB-Q) to form stable G-quadruplex structures in vitro was confirmed using 1H NMR, circular dichroism, UV spectroscopy, and thermal denaturation experiments. Moreover, the synthetic compound BOQ1 that shows a higher affinity for DNA forming quadruplex rather than duplex structures was found to bind with high affinity to the UpsB-Q.
  
  
  CONCLUSIONS
  This is the first demonstration of non-telomeric PQS in the genome of P. falciparum that form stable G-quadruplexes under physiological conditions in vitro. These results allow the generation of a novel hypothesis that the G-quadruplex sequences in the upstream regions of var genes have the potential to play a role in the transcriptional control of this major virulence-associated multi-gene family.
authors: Mass Spectrometry Laboratory, GIGA-Research, University of Liege, Liege, Belgium. nsmargiasso@ulg.ac.be
authors: Nicolas
authors: N
authors: Smargiasso
authors: Valérie
authors: V
authors: Gabelica
authors: Christian
authors: C
authors: Damblon
authors: Frédéric
authors: F
authors: Rosu
authors: Edwin
authors: E
authors: De Pauw
authors: Marie-Paule
authors: MP
authors: Teulade-Fichou
authors: J Alexandra
authors: JA
authors: Rowe
authors: Antoine
authors: A
authors: Claessens
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D002942:Circular Dichroism; D019295:Computational Biology; D016054:DNA, Protozoan / Q000235:genetics; D054856:G-Quadruplexes; D005786:Gene Expression Regulation; D008279:Magnetic Resonance Imaging; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan