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Title: Structure-guided design of immunomodulatory RNAs specifically targeting the cytoplasmic viral RNA sensor RIG-I
Authors: Yong, Hui Yee
Zheng, Jie
Ho, Victor Chin Yong
Nguyen, Mai Trinh
Fink, Katja
Griffin, Patrick R.
Luo, Dahai
Keywords: Science::Biological sciences
Issue Date: 2019
Source: Yong, H. Y., Zheng, J., Ho, V. C. Y., Nguyen, M. T., Fink, K., Griffin, P. R. & Luo, D. (2019). Structure-guided design of immunomodulatory RNAs specifically targeting the cytoplasmic viral RNA sensor RIG-I. FEBS Letters, 593(21), 3003-3014.
Project: OFIRG17nov084
NIGMS P50GM103368 (PRG)
Journal: FEBS Letters
Abstract: The cytoplasmic immune sensor RIG-I detects viral RNA and initiates an antiviral immune response upon activation. It has become a potential target for vaccination and immunotherapies. To develop the smallest but potent immunomodulatory RNA (immRNAs) species, we performed structure-guided RNA design and used biochemical, structural, and cell-based methods to select and characterize the immRNAs. We demonstrated that inserting guanosine at position 9 to the 10mer RNA hairpin (3p10LG9) activates RIG-I more robustly than the parental RNA. 3p10LG9 interacts strongly with the RIG-I helicase-CTD RNA sensing module and disrupts the auto-inhibitory interaction between the HEL2i and CARDs domains. We further showed that 3p10LA9 has a stronger cellular activity than 3p10LG9. Collectively, purine insertion at position 9 of the immRNA species triggered more robust activation of RIG-1.
ISSN: 0014-5793
DOI: 10.1002/1873-3468.13564
Rights: © 2019 Federation of European Biochemical Societies. All rights reserved. This paper was published by Wiley in FEBS Letters and is made available with permission of Federation of European Biochemical Societies.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles
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