Karpova A Y, Howley P M, Ronco L V
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genes Dev. 2000 Nov 15;14(22):2813-8. doi: 10.1101/gad.813800.
Interferon regulatory factors constitute a family of transcriptional activators and repressors involved in a large number of vital cellular processes. Interferon regulatory factor-3 (IRF-3) has been implicated in virus and double-stranded RNA mediated induction of IFNbeta and RANTES, in DNA damage signaling, and in virus-induced apoptosis. With its critical role in these pathways, the activity of IRF-3 is tightly regulated in myriad ways. Here we describe novel regulation of IRF-3 at the level of RNA splicing. We show that an unprecedented dual utilization of a splice acceptor/donor site within the IRF-3 mRNA governs the production of two alternative splice isoforms.
干扰素调节因子构成了一个转录激活因子和抑制因子家族,参与大量重要的细胞过程。干扰素调节因子3(IRF-3)与病毒和双链RNA介导的IFNβ及RANTES的诱导、DNA损伤信号传导以及病毒诱导的细胞凋亡有关。由于其在这些通路中的关键作用,IRF-3的活性受到多种方式的严格调控。在此,我们描述了IRF-3在RNA剪接水平上的新调控机制。我们发现,IRF-3 mRNA内一个剪接受体/供体位点前所未有的双重利用决定了两种可变剪接异构体的产生。