Natural antisense transcripts regulate gene expression in an epigenetic manner

Cytosine DNA methylation, covalent histone modifications, and RNA-mediated gene regulation are the major aspects of epigenetic regulation. Natural antisense transcripts (NATs), as a new member of regulatory RNAs, occur ubiquitously in prokaryote and eukaryote, and play significant roles in physiological or pathological processes. NATs, mostly non-coding RNAs, are involved in transcriptional interference, genomic imprinting, X inactivation, RNA editing, translational regulation, RNA export, DNA methylation, histone modifications, and so on. NATs regulate gene expression through direct interaction with the sense transcripts or indirect interaction with other targets, such as DNA methyltransferases, histone acetylases and histone deacetylases. There may be a direct link among NATs, DNA methylaton and histone modifications. Through formation of sense–antisense duplex structures, NATs exert a widespread impact on conventional gene expression at the mRNA and/or protein level and regulate sense transcripts in a concordant or discordant manner. As one of the important components in epigenetics, NATs could be a potentially rich source for scientists to exploit in the therapy of cancers and other diseases.