Right into the heart of microRNA-133a

Abstract

MicroRNAs play an essential role in diverse cellular processes, such as proliferation, differentiation, apoptosis, and stress response. Recent studies demonstrate that miRNAs are important for timing developmental decisions and fine-tuning cellular determination in vertebrate heart development. In an elegant set of experiments reported in this issue of Genes & Development, Liu et al. (3242-3254) demonstrate that miR-133a functions as an inhibitor of cardiomyocyte proliferation and a modifier of serum response factor (SRF)-dependent transcriptional signaling in the murine heart. Both targeted deletion and transgenic overexpression of miR-133a can result in the same cardiac phenotype, ventricular septal defect (VSD) and heart failure. The new data add another piece to the puzzle of regulatory networks that are implicated in cardiac disease. It will be interesting to see, if miR-133a is also involved in human heart diseases, especially VSD and dilated cardiomyopathy.

Figure 1.

Cardiac phenotypes of miR-133a and miR-1 knockout and transgenic mice. The bicistronic miRNAs miR-1 and miR-133a are transcribed by RNA Polymerase II (Pol II), processed from pri- to pre-miRNAs, and finally into mature miRNAs. The expression of miR-133a and miR-1 is regulated by SRF. MiR-133a directly targets SRF mRNA, forming a negative regulating feedback loop. The double knockout of miR-133a-1 and miR-133a-2 induces either lethal VSDs or DCM (DCM). Overexpression of miR-133a also leads to VSDs and cardiac hypoplasia. Similarly, overexpression of miR-1 results in hypoplastic hearts and consecutive heart failure, whereas the knockout of miR-1-2 leads to diverse phenotypes, including VSDs, DCM, or cardiac hyperplasia.