Short RNA molecules known as microRNAs (miRNAs) play a vital role in the regulation of gene expression. Anomalies in miRNAs expression and function have been implicated in pathological processes, such as the development of chronic diseases like atherosclerosis. The regulatory functions of miRNAs usually take place in the cytoplasm, where they interact with target RNA transcripts to inhibit their translation into protein or promote their decay. However, SyNergy member Professor Christian Weber’s group in the Institute for Cardiovascular Prevention (IPEK) at the LMU Medical Center has now described an exceptionally different mode of action. By investigating a miRNA named miR-126-5p, Weber’s team demonstrates that this molecule can unexpectedly be transferred into the cell nucleus and, by simply interacting with it, suppresses the activity of an enzyme, named caspase-3, which is responsible for killing the cell by programmed cell death. In this way, the molecule protects vascular integrity and reduces the extent of atherosclerotic lesions.