BMSE/MCDB Joint Seminar: *3PM* "What do ADARs do? Understanding the physiological functions of A-to-I RNA Editing"


Prof. Carl Walkley (Univ. of Melbourne) Host: Prof. Chuck Samuel

Date and Location

Wednesday October 14, 2020 3:00pm


The deamination of genomically encoded adenosine to inosine (A-to-I editing) in double-stranded RNA (dsRNA) by Adenosine Deaminase that act on RNA (ADAR) enzymes is a highly prevalent form of RNA base modification in higher eukaryotes. There are two active ADAR enzymes in mammals, ADAR1 and ADAR2. We have utilised murine genetics to understand the in vivo requirements for ADAR1 mediated A-to-I editing, focusing primarily on hematology. We previously demonstrated that ADAR1 was essential for the maintenance of both hematopoietic stem/progenitor populations and for normal erythropoiesis in vivo. This function was dependent upon the A-to-I editing activity of ADAR1. Genetic rescue studies, corroborated by multiple independent laboratories, has demonstrated that the primary physiological function of ADAR1 is to edit endogenous dsRNA substrates to prevent activation of the cytosolic innate immune system (MDA5//MAVS).

Most recently, we have used murine genetics to understand the extent of functional compensation between ADAR1 and ADAR2 in vivo, in particular in tissues where both are highly expressed such as the brain. In doing so, we have been able to define ADAR1 specific vs ADAR2 specific vs common editing sites in vivo. I will discuss the results from the studies and how they inform our understanding of the interplay of ADAR1 and ADAR2 and the physiological function of A-to-I editing in vivo. I will also discuss our ongoing work to understand how ADAR1 intersects with the cytosolic innate immune sensing system.