Epigenetic addition of m⁵C to HBV transcripts promotes viral replication and evasion of innate antiviral responses.

ABSTRACT: Eukaryotic five-methylcytosine (m⁵C) is an important regulator of viral RNA splicing, stability, and translation. However, its role in HBV replication remains largely unknown. In this study, functional m⁵C sites are identified in hepatitis B virus (HBV) mRNA. The m⁵C modification at nt 1291 is not only indispensable for Aly/REF export factor (ALYREF) recognition to promote viral mRNA export and HBx translation but also for the inhibition of RIG-I binding to suppress interferon-β (IFN-β) production. Moreover, NOP2/Sun RNA methyltransferase 2 (NSUN2) catalyzes the addition of m⁵C to HBV mRNA and is transcriptionally downregulated by the viral protein HBx, which suppresses the binding of EGR1 to the NSUN2 promoter. Additionally, NSUN2 expression cor

SUBMITTER: Ding S 

PROVIDER: S-EPMC10786922 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature