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.