Gene silencing.

Gene silencing has evolved in a broad range of organisms probably as defense mechanisms against invasive nucleic acids. Two major strategies are utilized. Transcriptional gene silencing (TGS) acts to prevent RNA synthesis and posttranscriptional gene silencing (PTGS) acts to degrade existing RNA. Although the final effects are similar, the mechanisms of TGS and PTGS are species specific. In most eukaryotes, gene silencing is associated with de novo DNA methylation. However, Caenorhabditis elegans shows an efficient PTGS-like mechanism but lacks a DNA methylation system. Additionally, key enzymes involved in plant and nematode PTGS, the cellular RNA-directed RNA polymerases, appear to be missing in Drosophila melanogaster. In this review, we discuss common features of TGS and PTGS that have been identified across species but for TGS we will concentrate only on methylation-mediated gene inactivation. This effort is complicated by the vague borders between gene silencing and normal gene regulation. Mechanisms that are involved in gene silencing are also used to regulate controlled expression of endogenous genes. To outline the general aspects, gene silencing will be defined as narrowly as possible. The intention behind this review is to stimulate discussion and we seek to facilitate this by introducing speculative concepts that could lead to some reappraisal of the literature.