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

Interferon regulatory factor 5 (IRF5) is a key transcription factor regulating inflammatory cytokines and interferons, with its dysregulation linked to autoimmune and inflammatory diseases. Pseudogenes can exhibit gene regulatory functions. This study investigates the human IRF5 pseudogene 1 (IRF5P1) and its potential role in primate-specific innate immunity. We find that IRF5P1 is a chimeric processed pseudogene containing sequences derived from multiple sources and is specific to higher primates, such as apes and humans. Our analyses suggest that IRF5P1 arose through an ancient retroviral integration event, incorporating an IRF5-like sequence from a disparate organism. Interestingly, IRF5P1 resides within the triple QxxK/R motif containing (TRIQK) gene, and its antisense strand is predominantly expressed as part of the TRIQK pre-mRNA. We propose that the antisense IRF5P1 RNA may regulate IRF5 expression through complementary binding to the IRF5 mRNA, with variants in the IRF5 gene potentially modulating this interaction. The conservation of IRF5P1 in the primate lineage suggests its positive effects on primate evolution and innate immunity. This study highlights the importance of investigating pseudogenes and their potential regulatory roles in shaping lineage-specific immune adaptations.