GSE122543
Bud13 Promotes a Type I Interferon Response by Countering Intron Retention in Irf7
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. Overall design: mRNA profiles of mouse bone-marrow derived macrophages (BMDMs) expressing either knockdown shRNA or control.  Stimulations performed with TNFa, Poly(I:C), and CpG. Please note that the -Cyto and -Nuc (in the sample titles) indicates the fraction that was sequenced; '-Cyto' is mRNA from the cytoplasm and '-Nuc' is from the Nucleus. For the TNFa 0 mins - IFNa 120 mins samples, the raw data was simply mapped to generate the splicing data (provided in .tdf files).