Regulation of Mammalian Mobile DNA by RNA-Based Silencing Pathways
Harris Soifer
from: RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity (Edited by: Kevin V. Morris). Caister Academic Press, U.K. (2008)
Abstract
The field of RNA silencing has grown quickly in less than a decade from the unexpected observation of color variation in transgenic flowers to a conserved eukaryotic mechanism for regulating gene expression at the post transcriptional level. Genetic and biochemical dissection of RNA silencing processes in many eukaryotes indicate that multiple pathways operate to control the expression of target genes, often in a developmentally or tissue-specific manner. What has also become clear, however, is that specialization of RNA silencing components and trigger molecules that occurred during speciation has lead to differences in the regulation of target RNAs across species. In lower eukaryotes, such as Drosophila and C. elegans, where the study of RNA silencing processes has benefited greatly from ability to carry out targeted gene inactivation and large-scale genetic screens, the activity of mobile genetic elements within these genomes is under the direct control by one or more RNA-based silencing mechanisms. Mammalian genomes are dominated by retrotransposons, mobile genetic elements that move through an RNA intermediate and thus would seem to be obvious targets for an RNA-based silencing mechanism that relies on complementarity with the transcript. The idea that mammalian RNA silencing pathways function, in part, to regulate the activity of mobile genetic elements is supported by several empirical studies, although the mechanism of retrotransposon regulation by RNA appears to work by inducing DNA methylation at promoter sequences rather than through degradation of RNA. In this chapter, an overview of RNA silencing mechanisms in mammalian cells is presented along with an outline highlighting the different mobile genetic elements that inhabit the mouse and human genomes. A significant portion of the chapter is devoted to empirical evidence supporting a direct role for mammalian RNA silencing pathways in the regulation of mobile DNA. Furthermore, recent bioinformatic data suggesting that ancient mobile elements once regarded as "junk" have evolved into functional, non-coding RNA that serve as triggers for RNA-based gene regulation in mammalian cells are also discussed read more ...
