Role of endogenous antisense RNA in cardiac gene regulation.

Endogenous antisense RNA has been detected for a range of eukaryotic genes and now appears to be a common phenomenon in mammalian cells. Its abundance compared to levels of its complementary sense mRNA indicates that antisense RNA may be involved in posttrancriptional regulation of a gene. In general a downregulating effect on gene expression has been demonstrated or suggested. Due to the heterogeneity in origin and character of different antisense transcripts alternative functions such as stabilizing the corresponding sense transcript and being part of gene recombination must be considered. Regulation by endogenous antisense RNA has been shown for a plethora of genes, including cardiac genes, such as myosin heavy chainMHC, atrial light chain, and troponin I. There is now growing evidence that antisense transcription is involved in human disease, and it is reasonable to consider antisense as a target for intervention procedures. Here we review the progress in our understanding of as well as the controversies arising from investigating the regulatory mechanisms of antisense RNA, with special focus on cardiac genes. Finally, links between antisense transcription and heart disease and the possible use of antisense as a target of cardiac intervention procedures are discussed.