The mechanical regulation of RNA homeostasis in the failing heart

The mechanical regulation of RNA homeostasis in the failing heart

Abstract: The heart undergoes continuous adaptation to mechanical forces in a process known as cardiac remodelling. Modifications in the nanostructure and mechanics of extracellular matrix (ECM) parallel the progression of cardiac diseases, impairing cardiac cell function, progressively leading to organ failure. Excessive mechanical load is a primary driver of pathological cardiac remodelling, leading to heart failure (HF), a significant cause of morbidity and mortality worldwide. Emerging data suggest that RNA homeostasis can be influenced by mechanical cues, but the molecular mechanisms and players involved remain largely unknown.

During the seminar, I will discuss our previous research findings on the impact of pathological ECM remodelling occurring in HF on RNA metabolism by tuning the distribution and function of the RNA-binding protein hnRNPC. Furthermore, I will delve into my current work on the potential role of N6-methyladenosine RNA (m6A) modification as a mediator of heart mechanical responses.

Speaker: Dr Fabiana Martino

Biography: Dr. Fabiana Martino is a UKRI Postdoctoral Fellow at the National Heart and Lung Institute, Imperial College London. Her research focuses on altered RNA processes and molecular mechanisms of mechanotransduction contributing to cardiac dysfunction. Under the mentorship of Dr. Forte, Fabiana completed her PhD in Biomedical Sciences at the International Clinical Research Center and Masaryk University in Brno, Czechia, in 2020. During this time, she demonstrated that ECM remodelling occurring in heart failure serves as a switch in RNA homeostasis by tuning the distribution and function of a specific RNA-binding protein. In 2021, she moved to London to join the Emanueli group at Imperial College. Here, she secured an Individual Marie Curie fellowship to explore the interplay between N6-methyladenosin RNA modification and microRNAs in mediating heart mechanical responses, using living myocardial slices as a disease model in collaboration with Terracciano lab.

Host: Dr Giancarlo Forte