Document Type
Article
Publication Date
5-30-2003
Publication Title
The Journal of Biological Chemistry
Abstract
The transient control of diverse biological responses that occurs in response to varied forms of stress is often a highly regulated process. During the interferon (IFN) response, translational repression due to phosphorylation of eukaryotic initiation factor 2α, eIF2α, by the double-stranded RNA-dependent protein kinase, PKR, constitutes a means of inhibiting viral replication. Here we show that the transient nature of the IFN response against acute viral infections is regulated, at least in part, by RNase L. During the IFN antiviral response in RNase L-null cells, PKR mRNA stability was enhanced, PKR induction was increased, and the phosphorylated form of eIF2α appeared with extended kinetics compared with similarly treated wild type cells. An enhanced IFN response in RNase L-null cells was also demonstrated by monitoring inhibition of viral protein synthesis. Furthermore, ectopic expression of RNase L from a plasmid vector prevented the IFN induction of PKR. These results suggest a role for RNase L in the transient control of the IFN response and possibly of other cytokine and stress responses.
Recommended Citation
Khabar, Khalid S.A.; Siddiqui, Yunus M.; Al-Zoghaibi, Fahad; al-Haj, Latifa; Dhalla, Mohammed; Zhou, Aimin; Dong, Beihua; Whitmore, Mark; Paranjape, Jayashree; Al-Ahdal, Mohammed N.; Al-Mohanna, Futwan; Williams, Bryan R.G.; and Silverman, Robert H., "RNase L Mediates Transient Control of The Interferon Response Through Modulation of The Double-stranded RNA-Dependent Protein Kinase PKR" (2003). Chemistry Faculty Publications. 405.
https://engagedscholarship.csuohio.edu/scichem_facpub/405
DOI
10.1074/jbc.M208766200
Version
Publisher's PDF
Publisher's Statement
This research was originally published in Journal of Biological Chemistry. Khalid S. A. Khabar, Yunus M. Siddiqui, Fahad Al-Zoghaibi, Latifa Al-Haj, Mohammed Dhalla, Aimin Zhou, Beihua Dong, Mark Whitmore, Jayashree Paranjape, Mohammed N. Al-Ahdal, Futwan Al-Mohanna, Bryan R. G. Williams and Robert H. Silverman . RNase L Mediates Transient Control of The Interferon Response Through Modulation of The Double-stranded RNA-Dependent Protein Kinase PKR. Journal of Biological Chemistry. 2003; 278, 20124-20132. © the American Society for Biochemistry and Molecular Biology."
Volume
278
Issue
22
Comments
This work was supported in part by awards from the National Institutes of Health (NCI Grant CA44059 to R. H. S. and NIAID Grant AI343039 to B. R. G. W.) and the King Faisal Specialist Hospital and Research Center (to K. S. A. K.).