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.