Prediction of gene expression regulation by human microRNAs in Plasmodium falciparum.

Background: Malaria is a disease annually causing over 400,000 deaths. Deep understanding of molecular and genetic processes underlying its life cycle and pathogenicity is required to efficiently resist it. RNA interference is a mechanism of the gene expression regulation typical for a wide variety of species. Even though the existence of this phenomenon in Plasmodium falciparum has long been rejected, several recent works pose hypotheses and provide direct and indirect evidence of the existence of mechanisms similar to RNA interference in this organism. In particular, the possibility of regulation of P. falciparum gene expression through human microRNAs is of great importance both for fundamental biology and for medicine. In the present work we address the problem of possibility of the existence in the P. falciparum genome of the nucleotide sequences such that mRNAs transcribed from genes containing these sequences could form duplexes with human microRNAs. Using bioinformatics methods we have analysed genomes of 15 P. falciparum isolates for sequences homological to these microRNAs.

Results: The analysis has demonstrated the existence of a vast number of genes that could potentially be regulated by the human microRNAs in the plasmodial genome.

Conclusions: Despite the fact that the numbers of homological intervals vary significantly between isolates, the hsa-miR-451a and hsa-miR-223-3p microRNAs are expected to make the most notable contribution to the pathogenesis of P. falciparum malaria. The majority of homological intervals occur in genes encoding cell adhesion proteins.