Speaker: Ryan Boudreau, University of Iowa Health Care, Carver College of Medicine, Department of Internal Medicine, assistant professor of Internal Medicine - Cardiovascular Medicine
Title: MicroR NAs and microproteins in cardiac health and disease
Abstract: This seminar will overview two distinct research projects that are ongoing in the Boudreau Lab; both will touch on small things doing big things in biology (e.g., microRNAs and microproteins), as well as mitochondrial metabolism. Previously, we leveraged high-throughput biochemical means to construct the first transcriptome-wide map of microRNA (miR) binding sites in human heart. In examining the interface of this map with human genetic variation and heart failure outcomes, we discovered a miR-24 binding site within the SCN5A coding region (encodes the cardiac sodium channel Nav1.5) and found that its activity is modulated by an adjacent synonymous SNP (rs1805126). In humans, we linked the rs1805126 minor allele with decreased cardiac SCN5A expression and increased non-arrhythmic death in HF patients. We are currently exploring the mechanistic basis for these observations, using heterozygous SCN5A knockout mice, which we are finding to have altered mitochondrial metabolism and elevated oxidative stress in their hearts.
In recent work, we discovered that a heart- and muscle-enriched long, “non-coding” RNA actually does encode for a highly-conserved single-pass transmembrane micro-protein that localizes to the inner mitochondrial membrane; we named this protein “Mitoregulin” (Mtln). In gain- and loss-of-function studies, we found that Mtln “supercharges” mitochondria by increasing their 1) respiratory super-complex levels, 2) respiratory efficiencies, and 3) Ca2+ retention capacities, while reducing ROS. We are currently working to better define Mtln’s molecular function and assess if human genetic variation linked to Mtln expression associates with HF patient outcomes.
Host: Molecular, Cellular and Developmental Biology Graduate Student Organization