Abstract
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.