5’-triphosphate-dependent activation of PKR by RNAs with short stem-loops
Abstract
Molecular patterns in pathogenic RNAs can be recognized by the innate immune system, and a component of this response is the interferon-induced enzyme RNA-activated protein kinase (PKR). The major activators of PKR have been proposed to be long double-stranded RNAs. We report that RNAs with very limited secondary structures activate PKR in a 5'-triphosphate-dependent fashion in vitro and in vivo. Activation of PKR by 5'-triphosphate RNA is independent of RIG-I and is enhanced by treatment with type 1 interferon (IFN-alpha). Surveillance of molecular features at the 5' end of transcripts by PKR presents a means of allowing pathogenic RNA to be distinguished from self-RNA. The evidence presented here suggests that this form of RNA-based discrimination may be a critical step in mounting an early immune response.
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Several RNA structural features are immunostimulatory due to interactions with RNA sensors such as Toll-like receptors, RIG-I, and PKR.
“However, several RNA structural features have been described as immunostimulatory due to interactions with various RNA sensors such as Toll-like receptors, RIG-I, and PKR.”
From Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals (2015) · cites this paper as [14]
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- Authors
- Nallagatla, S. R., Hwang, J., Toroney, R., Zheng, X., Cameron, C. E., & Bevilacqua, P. C.
- Affiliations
- Pennsylvania State University (US)
- Corresponding author
- Nallagatla, Subba Rao
- Hwang, Jungwook
- Cameron, Craig E.
- Bevilacqua, Philip C.
- Venue
- Science
- Published
- 2007-11-30
- Volume
- 318
- Issue
- 5855
- Pages
- 1455-1458
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1973179284
- Cited by
- 222
- References
- 21
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 9 · 2022: 7 · 2021: 7 · 2020: 7 · 2019: 12 · 2018: 9 · 2017: 7 · 2016: 15 · 2015: 16 · 2014: 8 · 2013: 18 · 2012: 18
- FWCI
- 6.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM058709, GM58709)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- PKR activation, 5'-triphosphate RNA, RNA secondary structure, RIG-I, type I interferon, interferon-alpha, double-stranded RNA, antiviral innate immunity
- MeSH terms
- DEAD Box Protein 58, Animals, Base Sequence, Chlorocebus aethiops, Enzyme Activation, Humans, Immunity, Innate, Molecular Sequence Data, Nucleic Acid Conformation, Phosphoric Monoester Hydrolases, Polyphosphates, Receptors, Immunologic, RNA, RNA, Double-Stranded, Transfection, Vero Cells, Eukaryotic Initiation Factor-2, Interferon-alpha, Interferon-beta, eIF-2 Kinase, Cell Line, Tumor, DEAD-box RNA Helicases
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