ACE2 is a transmembrane receptor located in cells in various tissues around the body. Its normal role is the conversion of Angiotensin II to Angiotensin 1-7 leading to vasodilation and a subsequent reduction in blood pressure via the renin-angiotensin-aldosterone system. ACE2 also plays a pivotal role in the infection of COVID-19 as it determines entry of virus into human cells. SARS-CoV-2 uses one of its four structural proteins, the spike (S) glycoprotein, to bind to the ACE2 receptor. This entry into the cell begins the process of infection and spread of the disease; because of the abundance of ACE2 throughout the body, viruses are able to enter a number of different organs. This multi-cell-entry via ACE2 is why COVID-19 affects multiple organ systems in the human body. Currently, therapies targeting ACE2 expression are limited. MicroRNA (miRNA)s are short non-coding RNA that downregulate the expression of a variety of proteins, and therefore offer a mechanism by which to inhibit the expression of ACE2. MiRNAs can potentially downregulate ACE2 protein synthesis by binding to the mRNA of ACE2 at a seed sequence. This binding results in mRNA degradation or inhibition of translation. Thus, our goal was to identify miRNA that may potentially target and downregulate ACE2. TargetScan, DIANA-MicroT, and PicTar are three algorithms that predict miRNAs that can bind to the mRNA of ACE2 and downregulate its expression. Together, the prediction tools resulted in 57 shared human miRNAs that target ACE2. We then utilized self-defined parameters to narrow down our list and identified hsa-miR-4520-2-3p as our predicted miRNA to target ACE2. This miRNA will be experimentally verified in the future.
Supervisor: Prof Nipun Chopra, PhD
Ruggles, Molly and Chopra, Nipun, "Hsa-miR-4520-2-3p: A Potential Modulator of COVID-related ACE2" (2020). Science Research Fellows Posters. 43.