Team

SmORFs and Microproteins in Drosophila

Team manager: Jennifer Zanet

Presentation

When genomes were sequenced and annotated, ORFs of less than 100 codons (small ORF or smORF) were not considered in order to avoid false gene annotations. However, the recent discovery of alleged non-coding RNAs (ncRNAs) capable of coding for microproteins less than 100aa from their unannotated smORFs brought to light a new population of unknown molecules. These small proteins translated from smORFs have different names: microproteins, smORF peptides, micropeptides, SEP or AltORF. The development of high-throughput techniques dedicated to identifying putative encoding smORFs has led to the identification of thousands of smORFs, among millions, in all genomes. Only a fraction of the microproteome has been explored suggesting that it constitutes an overlooked reservoir of biological regulators. We have started to work on the pioneer Pri peptides since the emergence of the microprotein field and deciphered their molecular mode of action in different tissues at different stages of Drosophila development.

At present, we identify novel bioactive microproteins which control developmental processes and reproductive functions using Drosophila as an in vivo animal model. By combining cell imaging, molecular genetics, transcriptomic and proteomic approaches, we aim to decipher the molecular function of microproteins in vivo.

Projet 1

Projet 2

Team members

– Chanut-Delalande, H. and Zanet, J. (2024). Small ORFs, Big Insights: Drosophila as a Model to Unraveling Microprotein Functions. Cells 13, 1645.

– Gallois, M., Menoret, D., Marques-Prieto, S., Montigny, A., Valenti, P., Moussian, B., Plaza, S., Payre, F. and Chanut-Delalande, H. (2024). Pri peptides temporally coordinate transcriptional programs during epidermal differentiation. Science Advances 10, eadg8816.

– Markus, D., Pelletier, A., Boube, M., Port, F., Boutros, M., Payre, F., Obermayer, B. and Zanet, J. (2023). The pleiotropic functions of Pri smORF peptides synchronize leg development regulators. PLOS Genetics 19, e1011004.

– Dib, A., Zanet, J., Mancheno-Ferris, A., Gallois, M., Markus, D., Valenti, P., Marques-Prieto, S., Plaza, S., Kageyama, Y., Chanut-Delalande, H., et al. (2021). Pri smORF Peptides Are Wide Mediators of Ecdysone Signaling, Contributing to Shape Spatiotemporal Responses. Front. Genet. 12, 714152.

– Zanet, J., Chanut-Delalande, H., Plaza, S. and Payre, F. (2016). Small Peptides as Newcomers in the Control of Drosophila Development. In Current Topics in Developmental Biology, pp. 199–219. Elsevier.

– Zanet, J., Benrabah, E., Li, T., Pélissier-Monier, A., Chanut-Delalande, H., Ronsin, B., Bellen, H. J., Payre, F. and Plaza, S. (2015). Pri sORF peptides induce selective proteasome-mediated protein processing. Science 349, 1356–1358.

– Chanut-Delalande, H., Hashimoto, Y., Pelissier-Monier, A., Spokony, R., Dib, A., Kondo, T., Bohère, J., Niimi, K., Latapie, Y., Inagaki, S., et al. (2014). Pri peptides are mediators of ecdysone for the temporal control of development. Nat Cell Biol 16, 1035–1044.

Funding

Affiliation