Antisense transcription: A critical look in both directions

The mammalian genome contains a large layer of hidden biological information. High-throughput methods have provided new insights into the regulatory networks that orchestrate the when, where and how of gene expression, revealing a complex interplay between proteins, regulatory RNAs, and chemical and structural alterations of the genome itself. Naturally occurring antisense transcription has been considered as an important feature in creating transcriptional and hence cellular and organismal complexity. Here, we review the current understanding of the extent, functions and significance of antisense transcription. We critically discuss results from genome-wide studies and documented examples of individual antisense transcripts. So far, the regulatory potential of gene overlaps has been demonstrated only in a few selected cases of experimentally characterized antisense transcripts. Facing the large-scale antisense transcription observed in eukaryotic genomes, it still remains an open challenge to distinguish transcriptional noise from biological function of gene overlapping patterns.