Post-transcriptional regulation of antiviral gene expression by N6-methyladenosine.

Type I interferons (IFNs) induce hundreds of IFN-stimulated genes (ISGs) in response to viral infection. Induction of these ISGs must be regulated for an efficient and controlled antiviral response, but post-transcriptional controls of these genes have not been well defined. Here, we identify a role for the RNA base modification N6-methyladenosine (m ⁶ A) in the regulation of ISGs. Using ribosome profiling and quantitative mass spectrometry, coupled with m ⁶ A-immunoprecipitation and sequencing, we identify a subset of ISGs, including IFITM1, whose translation is enhanced by m ⁶ A and the m ⁶ A methyltransferase proteins METTL3 and METTL14. We further determine that the m ⁶ A reader YTHDF1 increases the expression of IFITM1 in an m ⁶ A-binding-dependent manner. Importantly, we find that the m ⁶ A methyltransferase complex promotes the antiviral activity of type I IFN. Thus, these studies identify m ⁶ A as having a role in post-transcriptional control of ISG translation during the type I IFN response for antiviral restriction.
Competing Interests: Declaration of interests C.E.M. is a cofounder and board member for Biotia and Onegevity Health and an advisor or compensated speaker for Abbvie, Acuamark Diagnostics, ArcBio, Bio-Rad, DNA Genotek, Genialis, Genpro, Illumina, New England Biolabs, QIAGEN, Whole Biome, and Zymo Research.
(Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)