Year: 2021
Type: article
Abstract: 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.
Source: Cell Reports
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: National Aeronautics and Space Administration, Burroughs Wellcome Fund, American Heart Association, Vallee Foundation, Pershing Square Sohn Cancer Research Alliance, WorldQuant Foundation, National Institutes of Health, Weill Cornell Medical College, National Institute of Mental Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: Elucidating mechanisms of microRNA pathway deregulation in human cells, Understanding the role of N6-methyladenosine in hepatitis C virus infection, G3376477779, Mapping the RNA modification N6-methyladenosine during Zika virus infection, Viral Oncology Training Grant, The Spatiotemporal Landscape of the Human Brain Epitranscriptome, G6023573817, Weill Cornell/Rockefeller/Sloan Kettering MST Program, Defining the role of the RNA modification N6-methyladenosine during Flaviviridae virus infection
OpenAlex ID: W3133744017