Deciphering the functions of alternative proteins produced from “non-coding RNAs” in growth and reproduction – AltFUNC

Genome annotations have been based on several main criteria to distinguish “true” ORFs from random events including a minimum length of 100 codons. Recent studies have showed that several genes predicted to be non-coding actually encode sequences for the production of active small polypeptides of less than 100 amino acids, called alternative proteins (or AltProts). Several AltProts were shown to be biologically active molecules. They seem to be involved in a wide range of biological functions and regulate key cellular processes. Due to their large spectrum of functions, AltProts represent attractive new tools for drug development and agricultural applications.
Despite the prediction of thousands of AltProts among several species, only hundreds of them have been validated so far. The roles of fewer AltProts, less than 50 across all species, have been characterized in details. We recently performed a deep analysis of the alternative proteome of Drosophila melanogaster identifying 52 new AltProts produced from RNAs previously annotated as « long non-coding RNAs » (lncRNAs). Interestingly, 12 of them are expressed mainly in adult male semen-secreting cells suggesting that they might be involved in reproduction. In addition, we identified a new AltProt, named miPEP14, as important for standard growth of the organism. The combination of transcriptomics and interactome data points toward a role of miPEP14 in the regulation of the ecdysone and insulin pathways, two antagonist hormones well known to regulate body size growth. So far, no link was established between AltProts and these biological processes.
The aim of the AltFUNC project is to investigate the functions of AltProts produced from previously annotated lncRNAs in growth and reproduction. We will use the model organism Drosophila melanogaster to explore the role of AltProts in these biological processes. We will precise the role of miPEP14 associated to the ecdysone and insulin pathways and characterize the functions of newly identified AltProts encoded by lncRNAs in Drosophila melanogaster reproduction thanks to a combination of interactome and genetics approaches.