ArticlebioRxiv : the preprint server for biology2025
Short 5' UTRs serve as a marker for viral mRNA translation inhibition by the IFIT2-IFIT3 antiviral complex.
Dustin R Glasner, Candace Todd, Brian Cook, Agustina D'Urso, Shivani Khosla, Elena Estrada, Jaxon D Wagner, Mason D Bartels, Pierce Ford, Jordan Prych and 12 more
Abstract readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
22 authors.
Candace ToddSchool of Biological Sciences, University of California, San Diego, CA, USA.
Agustina D'UrsoSchool of Biological Sciences, University of California, San Diego, CA, USA.
Elena EstradaSchool of Biological Sciences, University of California, San Diego, CA, USA.
Mason D BartelsTherapeutic Innovation Center, Baylor College of Medicine, Houston, Texas, USA.
Jordan PrychSchool of Biological Sciences, University of California, San Diego, CA, USA.
Brian A YeeDepartment of Cellular and Molecular Medicine, University of California, San Diego, CA USA.ORCID 0000-0001-5615-8550 Kaori M EgoDepartment of Cellular and Molecular Medicine, University of California, San Diego, CA USA.
Sarah R HollandSchool of Biological Sciences, University of California, San Diego, CA, USA.
James Brett CaseDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0001-7331-5511 Michael S DiamondDepartment of Medicine, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0002-8791-3165 Gene W YeoDepartment of Cellular and Molecular Medicine, University of California, San Diego, CA USA.ORCID 0000-0002-0799-6037 Funding
Functional RNA elements in the human genomeR01HG004659 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kevin Daniel Corbett, Eugene Wei-Ming Yeo · 2008 to 2026
$12.4MPathways in Biological Sciences Training ProgramT32GM133351 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Matthew Daugherty, Randolph Y. Hampton · 2020 to 2026
$9.9MTechnology Development Coordinating CenterU24HG011735 · NHGRI · JACKSON LABORATORY · PI Mark D ADAMS · 2021 to 2026
$8.1MA comprehensive binding and functional map of human RNA-binding proteinsU24HG009889 · NHGRI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI GRAVELEY, BRENTON R., YEO, EUGENE WEI-MING · 2022 to 2025
$5.5MSTAMP technology to enable single-cell and isoform-sensitive detection of RBP sitesR01HG011864 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YEO, EUGENE WEI-MING · 2021 to 2024
$4.0MPathogen-driven evolution of innate antiviral defense mechanismsR35GM133633 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Matthew Daugherty · 2019 to 2026
$3.3MMolecular mechanisms of nucleic acid recognition and maintenance in meiosis and innate immunityR35GM144121 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kevin Daniel Corbett · 2022 to 2026
$2.7MRibo-STAMPEDE: novel tools for molecular profiling of brain cell typesRF1MH126719 · NIMH · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPPI, GIORDANO, YEO, EUGENE WEI-MING · 2022 to 2022
$2.3MRobust, high-throughput identification of RNA processing regulators and regulatory networks genome-wideR00HG009530 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI VAN NOSTRAND, ERIC LYMAN · 2020 to 2022
$747kConsequences of IFIT Gene Evolution on Species-Specific Antiviral ImmunityK22AI119017 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DAUGHERTY, MATTHEW · 2016 to 2017
$267kNHGRI NIH HHS R00 HG009530NHGRI NIH HHS R01 HG004659NHGRI NIH HHS R01 HG011864NHGRI NIH HHS U24 HG009889NHGRI NIH HHS U24 HG011735NIAID NIH HHS K22 AI119017NIGMS NIH HHS R35 GM133633NIGMS NIH HHS R35 GM144121NIGMS NIH HHS T32 GM133351NIMH NIH HHS RF1 MH126719
6 · The paper itselfAbstract
Recognition of "non-self" nucleic acids, including cytoplasmic dsDNA, dsRNA, or mRNAs lacking proper 5' cap structures, is critical for the innate immune response to viruses. Here, we demonstrate that short 5' untranslated regions (UTRs), a characteristic of many viral mRNAs, can also serve as a molecular pattern for innate immune recognition via the interferon-induced proteins IFIT2 and IFIT3. The IFIT2-IFIT3 heterodimer, formed through an intricate domain swap structure resolved by cryo-EM, mediates viral mRNA 5' end recognition, translation inhibition, and ultimately antiviral activity. Critically, 5' UTR lengths <50 nucleotides are necessary and sufficient to sensitize an mRNA to translation inhibition by the IFIT2-IFIT3 complex. Accordingly, diverse viruses whose mRNAs contain short 5' UTRs, such as vesicular stomatitis virus and parainfluenza virus 3, are sensitive to IFIT2-IFIT3-mediated antiviral activity. Our work thus reveals a pattern of antiviral nucleic acid immune recognition that takes advantage of the inherent constraints on viral genome size.
Indexed as
host-virus interactionsIFIT proteinsInnate antiviral immunityinterferon-stimulated genesnon-self RNA recognitionviral mRNA translation
Identifiers
PMID39990370
PMCPMC11844544
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