Bud13 Promotes a Type I Interferon Response By Countering Intron Retention in Irf7
Abstract
Intron retention (IR) has emerged as an important mechanism of gene expression control, but the factors controlling IR events remain poorly understood. We observed consistent IR in one intron of the Irf7 gene and identified BUD13 as an RNA-binding protein that acts at this intron to increase the amount of successful splicing. Deficiency in BUD13 was associated with increased IR, decreased mature Irf7 transcript and protein levels, and consequently a dampened type I interferon response, which compromised the ability of BUD13-deficient macrophages to withstand vesicular stomatitis virus (VSV) infection. Global analysis of BUD13 knockdown and BUD13 cross-linking to RNA revealed a subset of introns that share many characteristics with the one found in Irf7 and are spliced in a BUD13-dependent manner. Deficiency of BUD13 led to decreased mature transcript from genes containing such introns. Thus, by acting as an antagonist to IR, BUD13 facilitates the expression of genes at which IR occurs.
Additional Information
© 2018 Published by Elsevier Inc. Received 12 June 2018, Revised 20 October 2018, Accepted 29 November 2018, Available online 10 January 2019. The authors would like to thank Mario Blanco and Mitchell Guttman (Department of Biology, California Institute of Technology) for assistance with eCLIP analysis and Patricia Turpin, Mati Mann, Guideng Li, and Alok Joglekar (Department of Biology, California Institute of Technology) for experimental and computational assistance. Additionally, the authors would like to thank Genhong Cheng (Department of Microbiology, Immunology & Molecular Genetics, UCLA) for VSV and Jae Jung (Department of Molecular Microbiology & Immunology, USC) for VSV-GFP. This work was funded by the NIH (grant 5R21AI126344) and an endowment provided by the Raymond and Beverly Sackler Foundation. Data and Software Availability: All next-generation sequencing data reported in this study is depsited in the Gene Expression Omnibus database under accession number GSE122543. Author Contributions: L.F, D.M., and D.B. conceived and designed experiments. L.F. conducted experiments. C.B. helped develop RAP-MS and knockdown experiments. L.F. and D.M. analyzed sequencing data. A.M. oversaw mass spectrometry, and M.J.S. performed mass spectrometry analysis. L.F, D.M., and D.B. wrote the manuscript with input from all authors. The authors declare no competing interests.Attached Files
Submitted - 443820.full.pdf
Supplemental Material - 1-s2.0-S109727651831030X-mmc1.pdf
Supplemental Material - 1-s2.0-S109727651831030X-mmc2.xls
Supplemental Material - 1-s2.0-S109727651831030X-mmc3.xls
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Additional details
- Eprint ID
- 90484
- Resolver ID
- CaltechAUTHORS:20181029-162149332
- 5R21AI126344
- NIH
- Raymond and Beverly Sackler Foundation
- Created
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2018-10-30Created from EPrint's datestamp field
- Updated
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2023-06-01Created from EPrint's last_modified field