Serine/arginine-rich splicing factor 7 promotes the type I interferon response by activating Irf7 transcription. Academic Article uri icon

abstract

  • Tight regulation of macrophage immune gene expression is required to fight infection without risking harmful inflammation. The contribution of RNA-binding proteins (RBPs) to shaping the macrophage response topathogens remains poorly understood. Transcriptomic analysis reveals that a member of the serine/arginine-rich (SR) family of mRNA processing factors, SRSF7, is required for optimal expression of a cohort of interferon-stimulated genes in macrophages. Using genetic and biochemical assays, we discover that in addition to its canonical role in regulating alternative splicing, SRSF7 drives transcription of interferon regulatory transcription factor 7 (IRF7) to promote antiviral immunity. At the Irf7 promoter, SRSF7 maximizes STAT1 transcription factor binding and RNA polymerase II elongation via cooperation with the H4K20me1 histone methyltransferase KMT5a (SET8). These studies define a role for an SR protein in activating transcription and reveal an RBP-chromatin network that orchestrates macrophage antiviral gene expression.

published proceedings

  • Cell Rep

altmetric score

  • 12.45

author list (cited authors)

  • Scott, H. M., Smith, M. H., Coleman, A. K., Armijo, K. S., Chapman, M. J., Apostalo, S. L., ... Patrick, K. L.

citation count

  • 0

complete list of authors

  • Scott, Haley M||Smith, Mackenzie H||Coleman, Aja K||Armijo, Kaitlyn S||Chapman, Morgan J||Apostalo, Summer L||Wagner, Allison R||Watson, Robert O||Patrick, Kristin L

publication date

  • February 2024