RNA m⁶ A modification enzymes shape innate responses to DNA by regulating interferon β.

ABSTRACT: Modification of mRNA by N⁶-adenosine methylation (m⁶A) on internal bases influences gene expression in eukaryotes. How the dynamic genome-wide landscape of m⁶A-modified mRNAs impacts virus infection and host immune responses remains poorly understood. Here, we show that type I interferon (IFN) production triggered by dsDNA or human cytomegalovirus (HCMV) is controlled by the cellular m⁶A methyltrasferase subunit METTL14 and ALKBH5 demethylase. While METTL14 depletion reduced virus reproduction and stimulated dsDNA- or HCMV-induced IFNB1 mRNA accumulation, ALKBH5 depletion had the opposite effect. Depleting METTL14 increased both nascent IFNB1 mRNA production and stability in response to dsDNA. In contrast, ALKBH5 depletion reduced nascent

SUBMITTER: Rubio RM 

PROVIDER: S-EPMC6295168 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature