ABSTRACT
The utility of small RNAs to modulate the transcription of specific
target genes in mammalian cells is an exciting recent development
with implications for our understanding of endogenous transcrip-
tional control, the development of novel RNA-based therapeutics,
and the study of gene function. Both transcriptional gene silencing
(TGS) and transcriptional gene activation (TGA) have been reported.
In the case of TGS, small RNAs targeting promoter regions either
recruit epigenetic modifying complexes to a promoter-associated
RNA in order to induce silent-state chromatin modifications and
DNA methylation or sterically inhibit RNA polymerase procession
via direct interaction with chromosomal DNA. Conversely, in
the case of TGA, targeting antisense RNA transcripts relieves
endogenous epigenetic silencing, leading to an increase in target
gene expression. Noncoding RNA transcripts appear to be involved
in both transcriptional silencing and activation processes. Here we
describe the evidence that these processes occur in mammalian
cells, and discuss their utility in the treatment of human disease.