Regulation of gene expression by natural antisense RNA transcripts

The use of synthetic antisense oligonucleotides as specific inhibitors of gene expression exploits the susceptibility of mRNA to functional blockade at several levels, including mRNA processing, transport, translation and degradation. It is becoming increasingly apparent that the actions of these synthetic oligomers are analogous to those of endogenous RNA molecules involved in the regulation of gene expression in both prokaryotes and eukaryotes. A growing number of eukaryotic genes are now thought to be regulated at least in part by natural antisense RNA transcribed from the presumptive non-coding DNA strand. This possibility is supported by the presence of a complex system of double-stranded (ds) RNA-specific proteins and dsRNA-induced signal transduction pathways in eukaryotic cells. The presence of functional open reading frames in a number of recognized natural antisense RNA transcripts indicates that, in addition to regulating gene function at the RNA level, the antisense strand of many genes may code for as yet unidentified proteins. In the present study we review the current literature on the role(s) played by natural antisense RNA in eukaryotic cells, with an emphasis on genes for which clear evidence of regulation, or potential regulation by natural antisense RNA is available.