RNA interference in protozoan parasites and its application.

Abstract

RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression, via small RNA triggers derived from double-stranded RNA that can target specific genes; it is a natural process that plays a role in both the regulation of protein synthesis and in immunity. Discovery of RNAi by Fire and Mello in 1998 had a profound impact on unraveling novel aspects of eukaryotic biology. RNA interference (RNAi) has proven to be an immensely useful tool for studying gene function and validation of potential drug targets in almost all organisms. A great advance in parasitic protozoa was achieved by the experimental demonstration of RNAi in Trypanosoma brucei, and in other protists such as Leishmania braziliensis, Entamoeba histolytica and Giardia lamblia/intestinalis. These organisms exhibit numerous differences beyond the core 'dicer' and 'slicer' activities, thereby expanding knowledge of the evolutionary diversification of this pathway in eukaryotes. When present, RNAi has led to new technologies for engineering powerful and facile knockdowns in gene expression, revolutionizing biomedical research and opening clinical potentialities. In this review, we discuss the distribution of RNAi pathways, their biological roles, and experimental applications in protozoan parasites.