Extract: Natural antisense transcripts are endogenous transcripts that contain sequences that are complementary to other transcripts. Such complementary transcripts may be transcribed from opposing DNA strands at the same genomic locus (cis), or from different loci (trans), for example, pseudogenes. Notably, both types of antisense RNAs are genome-encoded and transcribed by DNA-directed RNA polymerases. A third putative source of antisense RNAs is transcription of the sense mRNA by an RNA-dependent RNA polymerase. Although only a few examples have been studied in detail, a significant number of naturally occurring antisense RNAs have been described in most eukaryotes, including mammals. Recent advances in bioinformatics have predicted as many as 2,500 mammalian cis-natural antisense transcripts. In one study, >2,600 human antisense transcripts were identified, of which >1600 were predicted to be true. 8% of the estimated 40,000 human genes were believed to have an antisense partner. Thus, it is likely that gene regulation by antisense transcription might be a common phenomenon in eukaryotic cells.