| Popis: |
While the signaling cascades and transcription factors that turn on expression of innate immune genes are well-characterized, the role of RNA binding proteins in activating and sustaining the innate immune response is poorly understood. Members of the serine/arginine-rich (SR) family of mRNA processing factors play diverse roles in transcription, pre-mRNA splicing, export, and translation. Transcriptomic analysis of murine macrophage cell lines revealed that one such SR protein, SRSF7, is required for optimal expression of interferon stimulated genes (ISGs) at rest and in response to a variety of innate immune stimuli in a splicing-independent fashion. We demonstrate that SRSF7 is necessary and sufficient to drive expression of interferon regulatory transcription factor 7 (IRF7), an important activator of the type I IFN response in resting and LPS-treated macrophages. By associating with theIrf7promoter, SRSF7 maximizes binding of the STAT1 transcription factor and promotes RNA polymerase II elongation. These studies define an unorthodox role for an SR protein in activating transcription and highlight the importance of RNA binding proteins in shaping the macrophage innate immune response to pathogens. |
