The Primate-Specific Presence of Interferon Regulatory Factor-5 Pseudogene 1

Interferon regulatory factor 5 (IRF5) is a critical transcription factor, regulating the production of inflammatory cytokines and interferons. Dysregulation of IRF5 has been linked to various autoimmune and inflammatory diseases. Pseudogenes may exhibit gene regulatory functions in various mechanisms. In this study, we find the human IRF5 pseudogene 1 (IRF5P1) is a chimeric processed pseudogene containing sequences derived from multiple sources. Remarkably, IRF5P1 is specific to higher primates such as apes and humans. We propose that IRF5P1 may have originated through the ancient integration of a retroviral sequence containing IRF5 mRNA from other animals. Interestingly, IRF5P1 overlaps with another gene, triple QxxK/R motif containing (TRIQK), and the antisense strand of IRF5P1 is predominantly expressed, likely as part of the TRIQK pre-mRNA. The antisense IRF5P1 RNA may regulate IRF5 expression through complementary binding to the IRF5 mRNA, and variants in the IRF5 gene may modulate this interaction. Our analysis suggests that IRF5P1 likely had positive effects on primate evolution, making IRF5P1 a favored component to maintain in the primate lineage, and rendering the pseudogene primate specific. Further studies are essential to elucidate the potential for IRF5P1 to participate in regulatory networks governing IRF5 activity and inflammation and innate immunity.