The RNA Binding Protein SRSF1 modulates Immune and Cancer pathways by regulating MyD88 transcription

Serine/Arginine splicing factor 1 (SRSF1), a member of the Serine/Arginine rich (SR) RNA-binding proteins (RBPs) family, regulates mRNA biogenesis at multiple steps and is deregulated in cancer and autoimmune diseases. Preliminary studies show that members of the SR protein family play a role in cellular transcription. We investigated SRSF1’s role in cellular gene transcription utilizing time-course RNA-Seq and nuclear run-on assays, validating a subset of genes transcriptionally regulated following SRSF1 overexpression. Pathway analysis showed that genes in the TNF/IL17 pathways were enriched in this dataset. Furthermore, we showed that MyD88, a strong activator of TNF transcription through transcription factors NF-κB and AP-1, is a primary target of SRSF1’s transcriptional activity. We propose that SRSF1 activates the transcription factors NF-κB and AP-1 through MyD88 pathway. SRSF1 overexpression regulates several genes that are deregulated in malignancies and immune disease, suggesting a role for SRSF1’s transcriptional activity in oncogenesis and immune response regulation.