Procreation is widely known to cause immunosuppression yet the mechanisms by which immunity is suppressed during peak fertility remain unknown.
tcer-1, which encodes the Caenorhabditis elegans homolog of the human transcription elongation and splicing factor, TCERG1, is once such gene involved in coordinating the immunity-fertility relationship. Our lab showed that TCER-1 is essential for healthy reproduction and prevention of age-related reproductive decline, and that it enhances lifespan in response to reproductive signals by ensuring lipid homeostasis. Our preliminary experiments have suggested that TCER-1 suppresses immunity, in part, through regulation of endogenous small RNA (smRNA) pathways. smRNA are short (~18-30nt) RNA molecules known for their ability to silence self and foreign genetic material to regulate host gene expression. Despite the fact endogenous smRNAs are reported to regulate immune-defense genes and microbes target host smRNA pathways during infection, little is known about the molecular mechanisms involved. We have discovered that loss-of-function mutations in biogenesis genes for endogenous small interfering RNAs (siRNAs) induce exceptional resistance against the human opportunistic pathogen Pseudomonas aeruginosa. Our epistasis analyses have demonstrated that these genes act in the same genetic pathway as TCER-1 to repress immunity. smRNA sequencing has also shown that
tcer-1 mutation causes a ~10% reduction in total endogenous siRNAs. These observations, and other data, have led us to hypothesize that TCER-1 suppresses innate immunity through modulation of the endogenous siRNA pathway and their targeted immunoresistance genes.