The RNA interference pathway from a trypanosome point of view

Abstract

In most eukaryotic cells expression or delivery of long double‐stranded RNA (dsRNA) signals the presence of foreign and/or potentially dangerous nucleic acids, such as viruses or transcripts derived from retroposons and transposons. As a consequence cells go on red alert and activate specific defense mechanisms to eliminate the invaders. Among such mechanisms is the RNA interference (RNAi) pathway, which is triggered by long dsRNAs, destroys target transcripts in a sequence‐specific manner and is widespread throughout eukaryotic evolution. In the late 90s our laboratory reported the discovery of RNAi in Trypanosoma brucei, a protozoan parasite that causes devastating diseases in sub‐Saharan Africa. Since then the way experiments are carried out in T. brucei has undergone a major revolution, and gene silencing by RNAi has found wide applications, including forward genetic screens and global analysis of gene function. I will present a historical recount of the discovery and mechanistic understanding of the trypanosome RNAi pathway with emphasis on its biological significance.