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Role of microRNAs in cardiac health and disease

MicroRNAs are a broad class of small non-coding RNAs that control diverse biological processes including major signaling pathways by regulating the expression of complementary target mRNAs. MicroRNAs were recently implicated in the regulation of diverse cardiac functions in a series of elegant genetic studies. Although these studies help to delineate the roles of microRNA in heart physiology, growth and morphogenesis, detailed molecular mechanisms for microRNAs in disease pathways in vivo are poorly understood. We have identified several candidate microRNAs which are severely deregulated in cardiac disease. We have established methodology for highly sensitive detection of microRNAs and quantification of their expression levels. We have cloned several human microRNA promotor sequences and determined the transcription factors driving expression of specific microRNAs. Techniques have been developed to manipulate microRNA expression in primary cells with synthetic precursors and inhibitors. Furthermore, microRNA expression is manipulated in vivo, in the living animal using targeted transgenesis and cholesterol-modified synthetic microRNA-inhibitors. (Thum, T. et al. Nature 456, 980–984, 2008) .