MicroRNAs in Cardiac Development and Function

Abstract

MicroRNAs (miRNAs) negatively regulate gene expression at the post‐transcriptional level, primarily by base‐pairing with the 3’‐untranslated region (3’‐UTR) of their target mRNAs. Many miRNAs are expressed in a tissue/organ‐specific manner and are associated with an increasing number of cell proliferation, differentiation and tissue development events.Cardiac muscle expresses distinct genes encoding structural proteins and a subset of signal molecules that control tissue specification and differentiation. The transcriptional regulation of cardiac and skeletal muscle development has been well established, yet only until recently has it been uncovered that miRNAs participate in the regulatory networks.A subset of miRNAs are either specifically or highly expressed in cardiac and skeletal muscle, providing an opportunity to understand how gene expression is controlled by miRNAs at the post‐transcriptional level in this muscle type. miR‐1, miR‐133, miR‐206 and miR‐208 have been found to be muscle‐specific, and thus have been called myomiRs. Our studies, using a conditional knockout strategy, show that microRNAs are essential for proper development and function of the heart. We further demonstrated that miR‐1 and miR‐133 play a vital role in myocyte proliferation and differentiation. Gain‐ and loss‐of‐function studies identify miR‐208a an important regulator of cardiac remodeling in response to stress.The discovery of myomiRs as a previously unrecognized component in the regulation of gene expression adds an entirely new layer of complexity to our understanding of cardiac, skeletal muscle development and function. Investigating myomiRs will not only reveal novel molecular mechanisms of the miRNA‐mediated regulatory network in cardiac and skeletal muscle development, but also raise new opportunities for therapeutic intervention for cardiovascular diseases.