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Alternative Splicing Coupled with Transcript Degradation Modulates OAS1g Antiviral Activity

Frankiw, Luke and Mann, Mati and Li, Guideng and Joglekar, Alok and Baltimore, David (2020) Alternative Splicing Coupled with Transcript Degradation Modulates OAS1g Antiviral Activity. RNA, 26 (2). pp. 126-136. ISSN 1355-8382. PMCID PMC6961538 . https://resolver.caltech.edu/CaltechAUTHORS:20191125-134707503

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1261/rna.073825.119DOIArticle
https://rnajournal.cshlp.org/content/26/2/126/suppl/DC1PublisherSupplemental Material
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6961538/PubMed CentralArticle
ORCID:
AuthorORCID
Li, Guideng0000-0003-0840-7262
Joglekar, Alok0000-0001-7554-7447
Baltimore, David0000-0001-8723-8190
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.
Funders:
Funding AgencyGrant Number
Raymond and Beverly Sackler FoundationUNSPECIFIED
Subject Keywords:AS-NMD; Alternative Splicing; Anti-viral response; Oligoadenylate synthetase; Post-transcriptional regulation
Issue or Number:2
PubMed Central ID:PMC6961538
Record Number:CaltechAUTHORS:20191125-134707503
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20191125-134707503
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:100036
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:25 Nov 2019 23:54
Last Modified:15 Apr 2020 21:32

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