RNA interference in protozoan parasites: achievements and challenges

Abstract

Protozoan parasites that profoundly affect mankind represent an exceptionally diverse group of organisms, including Plasmodium, Toxoplasma, Entamoeba, Giardia, trypanosomes, and Leishmania. Despite the overwhelming impact of these parasites, there remain many aspects to be discovered about mechanisms of pathogenesis and how these organisms survive in the host. Combined with the ever-increasing availability of sequenced genomes, RNA interference (RNAi), discovered a mere 13 years ago, has enormously facilitated the analysis of gene function, especially in organisms that are not amenable to classical genetic approaches. Here we review the current status of RNAi in studies of parasitic protozoa, with special emphasis on its use as a postgenomic tool.

Fig. 1.

The impact of RNAi in T. brucei. PubMed was queried for publications between January 1998 and the end of April 2011 that mention T. brucei. The resulting 3,543 citations were then searched for the terms “RNA interference,” “RNAi,” and “gene silencing”; the searches produced 525 (about 15%) citations. In the graphic shown, the numbers of RNAi citations in T. brucei studies are expressed as percentages of the total number of T. brucei publications in each year. Our analysis does not represent an attempt to capture all relevant publications but simply highlights a noteworthy trend.

Fig. 2.

RNAi in T. brucei. The Dicer-like enzymes DCL2 and DCL1 process long RNA duplexes (dsRNA) derived from sense and antisense transcripts from retroposons and repeats into siRNA duplexes in the nucleus and the cytoplasm, respectively. Argonaute (AGO1) is programmed with single-stranded “guide” siRNA, following siRNA strand separation, loading, and modification, to form the RNA-induced silencing complex, or RISC.