Regulation of inducible gene expression by natural antisense transcripts.

Natural antisense transcripts are frequently transcribed from many genes in eukaryotes. Although natural antisense transcripts have been recognized for a long time, their importance has been overlooked due to their heterogeneity, low expression level, and unknown function. Genes induced in responses to various external stimuli are transcriptionally regulated by the activation of a gene promoter and post-transcriptionally regulated by controlling mRNA stability and translatability. Recent studies have shed light on the functions of natural antisense transcripts at the post-transcriptional level. An antisense transcript may regulate gene expression with cis-controlling elements on the mRNA, and the antisense transcript itself may act in concert with trans-acting factors, including various proteins that bind to cis-controlling elements, drugs, and microRNAs. A novel mechanism recently reported to regulate mRNA stability includes the interaction of the antisense transcript with mRNA by hybridization to single-stranded loops in secondary structures. This antisense transcript-mediated post-transcriptional regulation may be one of the general mechanisms for the regulation of inducible gene expression and presents the possibility of the involvement of natural antisense transcripts in disease.