Catalytic RNA world relics in Dicer RNAs

RNA interference (RNAi) is a naturally occurring phenomenon of RNA-mediated gene silencingthat is highly conserved among multicellular organisms. In the first step of the pathway, long doublestrandedRNA molecules are chopped into shorter duplexes with 2 nucleotide overhangs at both 3’ ends byan endonuclease dubbed Dicer, the structure of which has been solved only recently. This results in theformation of small 21 nucleotide long RNAs, aptly named small or short interfering RNAs (siRNAs), whichare incorporated into a multimeric protein complex, the RNA-induced silencing complex (RISC). One of thetwo-siRNA strands guides RISC to a complementary RNA. After hybridization the endonucleolytic “slicer”activity of RISC cleaves the target RNA, thus preventing its translation. While long double-stranded RNAmolecules can be employed to induce RNAi in lower eukaryotes, siRNAs being 21 nucleotides in lengthhave to be used for gene silencing in mammalian cells in order to prevent the activation of an unspecificinterferon response [1]. In contrast to siRNAs, however, miRNAs are capable of inhibiting translation of thetargeted mRNA without degrading it (at least in mammalian cells)[2-4]. The need for in silico analysis of thecomponents of the RNA interference pathway arises from the fact that very little is known about thestructural and interacting properties of the components. With the above background the analysis wasperformed to identify putative catalytic motifs in the mRNA of the DICER enzyme.