Alternative Splicing Coupled with Transcript Degradation Modulates OAS1g Antiviral Activity
Abstract
At the heart of an innate immune response lies a tightly regulated gene expression program. This precise regulation is crucial because small changes can shift the balance from protective to destructive immunity. Here we identify a frequently used alternative splice site in the gene oligoadenylate synthetase 1g (Oas1g), a key component of the 2-5A antiviral system. Usage of this splice site leads to the generation of a transcript subject to decay, and removal of the site leads to increased expression of Oas1g and an improved antiviral response. However, removal of the splice site also leads to an increase in apoptotic cell death, suggesting this splicing event exists as a compromise between the pathogen protective benefits and collateral damage associated with OAS1g activity. Across the innate immune response, we show a multitude of alternative splicing events predicted to lead to decay exist and thus, have the potential to play a significant role in the regulation of gene expression in innate immunity.
Additional Information
© 2020 Frankiw et al. This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. Received October 29, 2019; Accepted November 13, 2019. Published in Advance November 18, 2019. The authors would like to thank Bert Semler (Department of Microbiology and Molecular Genetics, University of California, Irvine) for providing EMCV. The authors would also like to thank Megan Bergkessel (Department of Biology and Bioengineering, California Institute of Technology) and Prashant Bhat (Department of Biology and Bioengineering, California Institute of Technology) for experimental advice. This work was funded by an endowment provided by the Raymond and Beverly Sackler Foundation. Author contributions: L.F. and D.B. conceived and designed experiments with input from M.M., G.L., and A.J. L.F. conducted experiments and analyzed data. The manuscript was written by L.F. and D.B.Attached Files
Published - RNA-2020-Frankiw-126-36.pdf
Supplemental Material - Supplemental_Figures_Table.pdf
Files
Name | Size | Download all |
---|---|---|
md5:2b8af1028b92a55206039f386620a151
|
1.4 MB | Preview Download |
md5:f8e3171f3b5ff7ba5844b77e2fab7686
|
4.1 MB | Preview Download |
Additional details
- PMCID
- PMC6961538
- Eprint ID
- 100036
- DOI
- 10.1261/rna.073825.119
- Resolver ID
- CaltechAUTHORS:20191125-134707503
- Raymond and Beverly Sackler Foundation
- Created
-
2019-11-25Created from EPrint's datestamp field
- Updated
-
2023-07-21Created from EPrint's last_modified field
- Caltech groups
- Division of Biology and Biological Engineering