The MicroRNAs target mitochondrial dynamics and metabolism to regulate mitochondrial-mediated antiviral innate immunity

MicroRNAs (miRNAs) are short non-coding RNAs act as a suppressor of multiple genes and it is known that miRNAs link to numerous biological functions. Mitochondria act as a platform for innate immune response against RNA viruses via a mitochondrial outer membrane protein, MAVS. Here we report miR-302b and miR-372 involve in mitochondrial-mediated antiviral response. These miRNAs were upregulated by viral infection and influenced not only the production of type I interferon and inflammatory cytokines, but also mitochondrial function. Furthermore, we revealed that these phenotypes were induced by changing several mitochondrial genes expression. miR-302b induced mitochondrial fragmentation by changing gene expression related to mitochondrial dynamics to regulate Drp1 activity. Indeed, downregulation of SLC25A12 by miR-302b suppressed antiviral responses via inhibiting the MAVS activation directly. We first propose that miR-302b and miR-372 act as negative regulator of antiviral response by affecting mitochondrial function to inhibit excessive innate immune response. Change of gene expression by miR-302b in HEK293 cells was measured. The gene expression in the cells transfected with miR-302b mimic was compared with the cells transfected with negative control miRNA mimic.