5′-triphosphate-dependent activation of PKR by RNAs with short stem-loops

Subba Rao Nallagatla, Jungwook Hwang, Rebecca Toroney, Xiaofeng Zheng, Craig E. Cameron, Philip C. Bevilacqua

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170 Scopus citations

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-α). 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.

Original languageEnglish (US)
Pages (from-to)1455-1458
Number of pages4
JournalScience
Volume318
Issue number5855
DOIs
StatePublished - Nov 30 2007

All Science Journal Classification (ASJC) codes

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    Nallagatla, S. R., Hwang, J., Toroney, R., Zheng, X., Cameron, C. E., & Bevilacqua, P. C. (2007). 5′-triphosphate-dependent activation of PKR by RNAs with short stem-loops. Science, 318(5855), 1455-1458. https://doi.org/10.1126/science.1147347