ArticleNucleic acids research2014
Inhibition of translation by IFIT family members is determined by their ability to interact selectively with the 5'-terminal regions of cap0-, cap1- and 5'ppp- mRNAs.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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Who cites it
137 citing papers in PubMed, 195 citations in OpenAlex.
- Lost in translation: interferon-stimulated genes targeting flavivirus protein synthesis.Journal of virology · 2026Review
- Activating a B cell immune response regresses immunologically cold tumours.Nature nanotechnology · 2026Article
- The capping arms race: evolutionary interplay between IFIT proteins and viral molecular mimicry.Molecular biology reports · 2026Review
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- The promoting roles of GLP1R and GIPR in stemness maintenance and multiple lineage-specific differentiation of PDLSCs.Cellular & molecular biology letters · 2026Article
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- Functional RNA Elements in Alphavirus Genomes.Current microbiology · 2025Review
- Bat-specific adaptations in interferon signaling and GBP1 contribute to enhanced antiviral capacity.Nature communications · 2025Article
- A flexible, high-throughput system for studying live mRNA translation with HiBiT technology.Nucleic acids research · 2025Article
- The advent of clinical self-amplifying RNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Research progress of mosquito-borne virus mRNA vaccines.Molecular therapy. Methods & clinical development · 2025Review
- The Cap-proximal secondary structures of the 5'UTRs of parainfluenza virus 5 mRNAs specify differential sensitivity to type I interferon and IFIT1.The Journal of general virology · 2025Article
- RNA sensing at the crossroads of autoimmunity and autoinflammation.RNA (New York, N.Y.) · 2025Review
- Anatomical, subset, and HIV-dependent expression of viral sensors and restriction factors.Cell reports · 2025Article
- 5' terminal nucleotide determines the immunogenicity of IVT RNAs.Nucleic acids research · 2025Article
- An MST-based assay reveals new binding preferences of IFIT1 for canonically and noncanonically capped RNAs.RNA (New York, N.Y.) · 2025Article
- Technological breakthroughs and advancements in the application of mRNA vaccines: a comprehensive exploration and future prospects.Frontiers in immunology · 2025Review
- mRNA cancer vaccines from bench to bedside: a new era in cancer immunotherapy.Biomarker research · 2024Review
- Downregulation of the mThe Journal of biological chemistry · 2024Article
77 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Ribosomal recruitment of cellular mRNAs depends on binding of eIF4F to the mRNA's 5'-terminal 'cap'. The minimal 'cap0' consists of N7-methylguanosine linked to the first nucleotide via a 5'-5' triphosphate (ppp) bridge. Cap0 is further modified by 2'-O-methylation of the next two riboses, yielding 'cap1' (m7GpppNmN) and 'cap2' (m7GpppNmNm). However, some viral RNAs lack 2'-O-methylation, whereas others contain only ppp- at their 5'-end. Interferon-induced proteins with tetratricopeptide repeats (IFITs) are highly expressed effectors of innate immunity that inhibit viral replication by incompletely understood mechanisms. Here, we investigated the ability of IFIT family members to interact with cap1-, cap0- and 5'ppp- mRNAs and inhibit their translation. IFIT1 and IFIT1B showed very high affinity to cap-proximal regions of cap0-mRNAs (K1/2,app ∼9 to 23 nM). The 2'-O-methylation abrogated IFIT1/mRNA interaction, whereas IFIT1B retained the ability to bind cap1-mRNA, albeit with reduced affinity (K1/2,app ∼450 nM). The 5'-terminal regions of 5'ppp-mRNAs were recognized by IFIT5 (K1/2,app ∼400 nM). The activity of individual IFITs in inhibiting initiation on a specific mRNA was determined by their ability to interact with its 5'-terminal region: IFIT1 and IFIT1B efficiently outcompeted eIF4F and abrogated initiation on cap0-mRNAs, whereas inhibition on cap1- and 5'ppp- mRNAs by IFIT1B and IFIT5 was weaker and required higher protein concentrations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.