DOI: 10.1126/science.1147347. 5'-Triphosphate-Dependent Activation of PKR by RNAs with Short Stem-Loops

5'-Triphosphate-Dependent Activation of PKR by RNAs with Short Stem-Loops

10.1126/science.1147347

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

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.

Bibliography

Nallagatla, S. R., Hwang, J., Toroney, R., Zheng, X., Cameron, C. E., & Bevilacqua, P. C. (2007). 5â-Triphosphate-Dependent Activation of PKR by RNAs with Short Stem-Loops. Science, 318(5855), 1455â1458.

Authors 6

Subba Rao Nallagatla (first)
Jungwook Hwang (additional)
Rebecca Toroney (additional)
Xiaofeng Zheng (additional)
Craig E. Cameron (additional)
Philip C. Bevilacqua (additional)

References 24 Referenced 189

10.1146/annurev.biochem.67.1.227
T. E. Dever, A. C. Dar, F. Sicheri, in Translational Control in Biology and Medicine, M. B. Mathews, N. Sonenberg, J. W. Hershey, Eds. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 2007), pp. 319–344. / Translational Control in Biology and Medicine (2007)
10.1038/nrm1528
L. Manche, S. R. Green, C. Schmedt, M. B. Mathews, Mol. Cell. Biol.12, 5238 (1992). / Mol. Cell. Biol. (1992)
10.1021/bi9607259
10.1261/rna.7150804
10.1093/nar/15.21.8783
Materials and methods are available as supporting material on Science Online.
Fields Virology D. Knipe P. M. Howley Eds. (Lippincott Williams & Wilkins Philadelphia PA ed. 5 2007).
10.1128/jb.171.1.141-147.1989
10.1016/S0092-8674(01)00202-1
10.1038/nbt940
10.1016/j.bpc.2003.10.033
10.1016/j.cell.2005.06.044
10.1126/science.1132505
10.1126/science.1132998
10.1128/JVI.79.5.2689-2699.2005
10.1128/jvi.70.8.5611-5617.1996
10.1073/pnas.93.1.508
10.1021/bi980113j
10.1016/j.virusres.2005.10.014
10.1128/JVI.73.3.2425-2433.1999
10.1099/0022-1317-43-1-247
We thank B. Golden D. Herschlag and J. Reese for helpful comments and the following sources for funding: NIH grant GM58709 (P.C.B.) and the Martarano and Berg endowments of the Eberly College of Science (C.E.C.).

Dates

Type	When
Created	17 years, 9 months ago (Nov. 29, 2007, 5:33 p.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 3:39 a.m.)
Indexed	2 weeks, 4 days ago (Aug. 20, 2025, 8:33 a.m.)
Issued	17 years, 9 months ago (Nov. 30, 2007)
Published	17 years, 9 months ago (Nov. 30, 2007)
Published Print	17 years, 9 months ago (Nov. 30, 2007)

Funders 0

None

BibTeX

@article{Nallagatla_2007, title={5’-Triphosphate-Dependent Activation of PKR by RNAs with Short Stem-Loops}, volume={318}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1147347}, DOI={10.1126/science.1147347}, number={5855}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Nallagatla, Subba Rao and Hwang, Jungwook and Toroney, Rebecca and Zheng, Xiaofeng and Cameron, Craig E. and Bevilacqua, Philip C.}, year={2007}, month=nov, pages={1455–1458} }

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