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

Journal Article (Journal Article)

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 (m6A) in the regulation of ISGs. Using ribosome profiling and quantitative mass spectrometry, coupled with m6A-immunoprecipitation and sequencing, we identify a subset of ISGs, including IFITM1, whose translation is enhanced by m6A and the m6A methyltransferase proteins METTL3 and METTL14. We further determine that the m6A reader YTHDF1 increases the expression of IFITM1 in an m6A-binding-dependent manner. Importantly, we find that the m6A methyltransferase complex promotes the antiviral activity of type I IFN. Thus, these studies identify m6A as having a role in post-transcriptional control of ISG translation during the type I IFN response for antiviral restriction.

Full Text

Duke Authors

Cited Authors

  • McFadden, MJ; McIntyre, ABR; Mourelatos, H; Abell, NS; Gokhale, NS; Ipas, H; Xhemalçe, B; Mason, CE; Horner, SM

Published Date

  • March 2, 2021

Published In

Volume / Issue

  • 34 / 9

Start / End Page

  • 108798 -

PubMed ID

  • 33657363

Pubmed Central ID

  • PMC7981787

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2021.108798


  • eng

Conference Location

  • United States