Research Project
Non-canonical functions of microRNAs
We investigate the contribution of non-coding RNAs (ncRNAs) in cardiovascular physiology and pathology. We are particularly interested in mechanisms of regulation, trafficking, and function of ncRNAs in the maintenance of vascular homeostasis and their involvement in the development of vascular diseases, such as atherosclerosis. Our goal is to shed light on the relevance of ncRNAs in the development of vascular disease and to unveil their possible application as therapeutic or diagnostic/prognostic tools in patients with cardiovascular diseases.
MicroRNAs (miRNAs) are short (20-25 nucleotide long) ncRNAs mediating post-transcriptional repression of gene expression by pairing with target transcripts in RNA-induced silencing complexes (RISCs), where effector proteins promote decay or transcriptional repression. Our research provides evidence that miRNAs exert their functions also outside of this dogmatic mechanism. We provided the first evidence that miRNAs can directly affect protein functions by biophysical interactions. In particular, we reported how miR-126-5p in endothelial cells can engage in interactions with caspase-3 upon induction of autophagy (e.g., by protective high-shear stress). The binding to miR-126-5p inhibits the proteolytic activity of caspase-3 and limits apoptosis. This ultimately preserves endothelial integrity and protects against the development of atherosclerosis.
