Sex_And_SmORFs

Recent advances in omics unveiled that small ORF (smORF, under 100 codons) found in coding and non-coding RNAs can be translated into thousands of overlooked microproteins (under 100aa). While the microproteome represents an underexplored pool of novel developmental and cellular regulators, an important challenge is to define their function. Drosophila reproduction relies on inter-sex and inter-organ communication, with males transmitting essential signals during mating for female fertility. These signals induce physiological (organ remodeling) and behavioral changes, named Post Mating Response (PMR), that enhance fecundity. However, the key players involved in communication and organ remodeling are largely unknown. Given their small size, microproteins could be a source of long- and short-range signaling molecules participating in organ remodeling in reproduction. We identified two male microproteins, Tic and Tac, encoded by a bicistronic mRNA controlling the signals sent to the female during mating. Using the integrative Drosophila model that allows genetic manipulation and multi-level imaging, Sex_And_SmORFs aims to uncover actors of reproduction among the microproteins. Based on our complementary expertise in microprotein field, reproduction and proteomics, our consortium will 1) elucidate the molecular function of Tic and Tac in male reproductive organs, and 2) find the male microproteins triggering PMR in female. As the signals produced by the female that sustain fertility are unknown, we will 3) use spermatheca, the long-term sperm storage organ which undergoes remodeling to become highly secretive after mating, to find regulatory microproteins controlling organ remodeling and organ communication. Sex_And_SmORFs will uncover the functional diversity of microproteins, a largely unexplored family, and unravel short and long-range signaling molecules promoting insect reproduction, a concern for both agronomy and human health.