Cell Reports
Volume 34, Issue 9, 2 March 2021, 108798
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Article
Post-transcriptional regulation of antiviral gene expression by N6-methyladenosine

https://doi.org/10.1016/j.celrep.2021.108798Get rights and content
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Highlights

  • During the type I IFN response, many IFN-stimulated genes (ISGs) are modified by m6A

  • m6A promotes the expression of a subset of these ISGs by enhancing their translation

  • m6A augments the antiviral effects of the type I interferon response

Summary

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.

Keywords

N6-methyladenosine
m6A
Interferon
ISGs
YTHDF1
Translation

Cited by (0)

9

These authors contributed equally

10

These authors contributed equally

11

Present address: Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland

12

Present address: Department of Immunology, University of Washington, Seattle, WA 98109, USA

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Lead contact