ArticleNature chemical biology2009
Dynamic refolding of IFN-gamma mRNA enables it to function as PKR activator and translation template.
Article in Nature chemical biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 78 citations in OpenAlex.
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- mRNA vaccine sequence and structure design and optimization: Advances and challenges.The Journal of biological chemistry · 2025Review
- RNA recognition by PKR during DNA virus infection.Journal of medical virology · 2024Review
- RNA Activators of Stress Kinase PKR within Human Genes That Control Splicing or Translation Create Novel Targets for Hereditary Diseases.International journal of molecular sciences · 2024Article
- Gut ribotoxic stress responses facilitate dyslipidemia via metabolic reprogramming: an environmental health prediction.Theranostics · 2024Article
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- HIV co-opts a cellular antiviral mechanism, activation of stress kinase PKR by its RNA, to enable splicing of rev/tat mRNA.Cell & bioscience · 2023Article
- Adenovirus prevents dsRNA formation by promoting efficient splicing of viral RNA.Nucleic acids research · 2022Article
- Post-transcriptional control of T-cell cytokine production: Implications for cancer therapy.Immunology · 2021Review
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- Mucosal immunity and tRNA, tRF, and tiRNA.Journal of molecular medicine (Berlin, Germany) · 2021Review
- On the Way to Understanding the Interplay between the RNA Structure and Functions in Cells: A Genome-Wide Perspective.International journal of molecular sciences · 2020Review
- Human T cells employ conserved AU-rich elements to fine-tune IFN-γ production.European journal of immunology · 2020Article
- Long non-coding RNAeLife · 2020Article
- Tat IRES modulator of tat mRNA (TIM-TAM): a conserved RNA structure that controls Tat expression and acts as a switch for HIV productive and latent infection.Nucleic acids research · 2020Article
- Interactions between the 5' UTR mRNA of theRNA (New York, N.Y.) · 2020Article
- Stress Granules in the Post-transcriptional Regulation of Immune Cells.Frontiers in cell and developmental biology · 2020Review
- Crystal structure of an adenovirus virus-associated RNA.Nature communications · 2019Article
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7 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Interferon-gamma mRNA activates the RNA-dependent protein kinase PKR, which in turn strongly attenuates translation of interferon-gamma mRNA. Unlike riboswitches restricted to noncoding regions, the interferon-gamma RNA domain that activates PKR comprises the 5' UTR and 26 translated codons. Extensive interferon-gamma coding sequence is thus dedicated to activating PKR and blocking interferon-gamma synthesis. This implies that the PKR activator is disrupted by ribosomes during translation initiation and must refold promptly to restore PKR activation. The activator structure harbors an essential kink-turn, probably to allow formation of a pseudoknot that is critical for PKR activation. Three indispensable short helices, bordered by orientation-sensitive base pairs, align with the pseudoknot stem, generating RNA helix of sufficient length to activate PKR. Through gain-of-function mutations, we show that the RNA activator can adopt alternative conformations that activate PKR. This flexibility promotes efficient refolding of interferon-gamma mRNA, which is necessary for its dual function as translation template and activator of PKR, and which thus prevents overexpression of this inflammatory cytokine.
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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.