RNAi in the malaria parasite plasmodium

RNAi has emerged recently as one of the most promising tools in studying gene function (summarized in Chapter 1). It was initially believed to be based on an evolutionary defense mechanism of silencing RNA in eukaryotes to protect their genomes from exogenous (viral) and endogenous (transposon) elements. Related mechanisms with small RNAs are involved in cell homeostasis by regulating translation (Caenorhabditis elegans) and structure of heterochromatic domains in the genome. In many organisms, including C. elegans, Drosophila, zebra fish, and Xenopus, RNAi is activated by the presence of foreign dsRNA in the cell which triggers sequence-specific mRNA degradation. The dsRNA is enzymatically cleaved with the help of Dicer RNase III to give rise to small interfering RNA duplexes (siRNA). These siRNAs, usually 21 to 25 nucleotides in length and characterized by a two-nucleotide 3'-overhang, form a complex with a nuclease complex, the RNA-induced silencing complex (RISC), where they become unwound and aid in the homology-dependent degradation of the target RNA. Similar processes occur in plants as posttranscriptional gene silencing and cosuppression and quelling in fungi and algae. Plasmodium was the first intracellular organism in which RNAi was successfully demonstrated. Subsequent studies have shown that small RNAs may be used and that siRNAs are generated, but the mechanism of RNA silencing in Plasmodium has yet to be elucidated.