Symmetric arginine dimethylation is selectively required for mRNA splicing and the initiation of type I and type III interferon signaling

The goal of this study was to assess the extent of symmetric arginine dimethylation-dependent splicing and its associated signaling outcomes by using human T lymphocyte activation as a model system with a high rate of de novo transcription. Naïve human T lymphocytes were activated and treated with a selective inhibitor of PRMT5, PF-06829927, and investigated for changes in gene expression, alternative splicing, and chromatin accessibility. Human naïve CD3+ (ATAC), CD4+ or CD8+ (expression and splicing) T lymphocytes were activated for 72 (expression and splicing) or 96 (ATAC) hours with platebound anti-CD3, anti-CD28, IL-2, and either DMSO or PF-06829927