RNA-mediated gene silencing

Abstract

A number of gene-silencing phenomena including co-suppression discovered in plants, quelling in fungi and RNA interference in animals have been revealed to have steps in common. All occur in the cytoplasm at a post-transcriptional level with the mRNAs of target genes degraded in a sequence-specific manner. Small non-coding RNA molecules demonstrated to be mediators of these silencing phenomena have also been shown to mediate a parallel post-transcriptional gene silencing (PTGS) mechanism that regulates the expression of developmental genes, although in this latter mechanism, rather than being degraded, the translation of target mRNAs is inhibited. Both types of small RNA appear to be processed from longer double-stranded RNAs (dsRNAs) by a common endonuclease. RNAs may also operate as regulators of gene expression at a transcriptional level in the nucleus, via chromatin remodelling or RNA-directed DNA methylation. Methylation of promoter sequences leads to transcriptional gene silencing, while methylation of coding sequences by the same homology-dependent mechanism does not block transcription, but leads to PTGS. In some organisms, the RNA silencing signal may spread to other tissues inducing systemic RNA silencing.

DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression

“…The first exon and the first intron are hot spots of antisense RNA transcription, and antisense RNA TSS is preferentially observed in relatively long CGIs covering exon 1 and extending into intron 1 (Finocchiaro et al 2007). Both sense and antisense RNA play a role in gene expression by affecting DNA methylation status (Sleutels et al 2002;Pickford and Cogoni 2003;Imamura et al 2004). ChIPchip experiments on regions adjacent to the TSS have indicated that H3K4 methylation occurs in a 2-kb region downstream from the TSS and that the peaks in the region are located 1 kb downstream (Barski et al 2007).…”

Three genomes differentially contribute to the biosynthesis of benzoxazinones in hexaploid wheat

“…This discrepancy might be explained in terms of the reduction of translation efficiency caused by the increase of the TaBx transcripts in hexaploid wheat. Polyploidization might increase total transcription of genes, but, conversely, it might cause reduction in translation by some mechanisms, like small RNA-mediated or homology-dependent gene silencing as observed in plants with an overexpressing transgene homologous to the endogenous gene (40,41).…”

Heterochromatin?many flavours, common themes

“…It is also worth noting that, in plants, RNAi can directly induce DNA methylation, (17) but no such direct link has been established in mammals. It is also worth considering that to transcribe an RNA, a transcriptional activator is usually needed.…”