PT  - JOURNAL ARTICLE
AU  - Luke S. Frankiw
AU  - Devdoot Majumdar
AU  - Christian Burns
AU  - Logan Vlach
AU  - Annie Moradian
AU  - Michael J. Sweredoski
AU  - David Baltimore
TI  - Bud13 Promotes a Type I Interferon Response by Countering Intron Retention in Irf7
AID  - 10.1101/443820
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 443820
4099  - http://biorxiv.org/content/early/2018/10/15/443820.short
4100  - http://biorxiv.org/content/early/2018/10/15/443820.full
AB  - Intron retention (IR) has emerged as an important mechanism of gene expression control. Despite this, the factors that control 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 led to increased IR, decreased mature Irf7 transcript and protein levels, and consequently to a dampened type I interferon response. This impairment of Irf7 production in Bud13-deficient cells compromised their ability to withstand 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.