N⁶-methyladenosine modification enables viral RNA to escape recognition by RNA sensor RIG-I.

ABSTRACT: Internal N⁶-methyladenosine (m⁶A) modification is one of the most common and abundant modifications of RNA. However, the biological roles of viral RNA m⁶A remain elusive. Here, using human metapneumovirus (HMPV) as a model, we demonstrate that m⁶A serves as a molecular marker for innate immune discrimination of self from non-self RNAs. We show that HMPV RNAs are m⁶A methylated and that viral m⁶A methylation promotes HMPV replication and gene expression. Inactivating m⁶A addition sites with synonymous mutations or demethylase resulted in m⁶A-deficient recombinant HMPVs and virion RNAs that induced increased expression of type I interferon, which was dependent on the cytoplasmic RNA sensor RIG-I, and not

SUBMITTER: Lu M 

PROVIDER: S-EPMC7137398 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature