Dynamic A-to-I RNA editing in response to gut microbiome in honey bees

Abstract

ADAR-mediated adenosine-to-inosine (A-to-I) mRNA editing contributes to the proteomic diversity and behavioral complexity of animals. While recent studies indicate that the gut microbiome influences various aspects of animal behavior, the potential involvement of RNA editing in gut-brain interactions remains unexplored. Comparative transcriptomic analyses were performed between heads of germ-free (GF) versus conventional (CV) honey bees. A total of 1,528 A-to-I editing sites are identified in honey bee heads, among which nonsynonymous editing sites are overrepresented compared to random expectation. Overall editing levels are significantly downregulated in GF compared with CV, but Adar gene is not differentially expressed. However, Adar p.482 Ile>Met auto-recoding site, which is speculated to modulate Adar activity, is identified as a high-confidence differential editing site (DES) with decreased editing level in GF. Quantification of gut microbiota across 12 CV individuals reveals a significant positive correlation between p.482 Ile>Met editing level and Lactobacillus and Bombilactobacillus abundance. Colonization of a single bacterium Lactobacillus or Bombilactobacillus instead of Gilliamella in GF bees successfully restores the Adar p.482 Ile>Met and the global editing level. Our work demonstrates the complex and dynamic transcriptomic diversity exerted by A-to-I RNA editing, and discovers the axis of gut-Lactobacillus/Bombilactobacillus-brain-Adar-global RNA editing, providing an exciting scenario that gut microbiomes could impact RNA editing which might further facilitate phenotypic plasticity of social insects.