Abstract 11247: The Long Noncoding MALAT1 - MascRNA System is a Novel Regulator of Cardiac Innate Immunity

Background: Regarding disease pathogenesis, it has become evident that confinement to analysis of protein-coding regions of the genome is insufficient since many noncoding regions are associated with human diseases. We searched for elements of the noncoding genome influencing the highly variable course of a cardiomyopathy caused by a common single-stranded RNA virus (CVB3). Methods and Results: Transcriptome mapping of human CVB3 cardiomyopathy hearts showed high long noncoding RNAs (lncRNA) MALAT1 associated with spontaneous virus clearance and recovery, and low MALAT1 with virus persistence and clinical deterioration. Primary [[Unable to Display Character: ]]7kb MALAT1 transcript is only part of a complex RNA processing system generating e.g. mascRNA, a tRNA-like molecule, by a novel biosynthetic pathway. First, we found cell type-specific MALAT1 processing to result in grossly different mascRNA levels, which were highest in leukocytes. Second, CVB3 infection of genetically MALAT1-deficient (MAL...