Abstract
RNA silencing is a highly conserved mechanism found in both the plant and animal kingdoms that is thought to protect the genome from disruption by transposons and viral integration events. Double stranded RNAs (dsRNA) produced by transposons or replicating virus result in the production of short 21-25 nucleotide double stranded RNA molecules containing a hydroxyl group on a two base-pair 3' overhang and a 5' phosphate residue. These siRNAs are the hallmark of RNA silencing, also known as post transcriptional gene silencing (PTGS) in plants, quelling in Neurospora, and RNA interference in C. elegans, Drosophila, and Dictyostelium. Remarkably these siRNAs direct the degradation of the complementary target RNA through a complicated mechanism that is just now being understood. From our studies on RNA interference in Drosophila we propose a model in which the siRNAs interact through complementarity with the target RNA and are extended by a cellular RNA-dependent RNA polymerase (RdRP) to form a critical length of dsRNA that is subsequently degraded by RNase III-related enzymes. Here, we discuss this model and the data produced in Drosophila to support it and, in turn, this model is compared to the proposed scheme for RNA silencing in mammalian systems.
