MicroRNAs (miRNAs) are small regulatory RNAs previously thought not to be transcribed into polypeptides. We have recently shown that in plants primary transcripts of miRNAs encode and direct the synthesis of small, regulatory peptides, which we call miRNA-encoded peptides (miPEP)s (Lauressergues et al., 2015, Nature). MiPEPs are produced naturally by plants and enhance specifically the expression of their corresponding miRNAs. Moreover, external application of synthetic miPEPs to plants by watering or spraying increases the expression of miRNAs. This discovery of miPEPs has revealed the existence of a world of peptides more diverse and complex than previously thought, and probably with numerous important biological roles. The purpose of this project is to investigate this world of miPEP biology. We propose to analyse the molecular mechanisms underlying the effects of miPEPs as well as to develop methods to identify and analyse the diversity of small peptides in plants and animals. Finally, miPEPs provide a unique tool to attribute functions to all miRNAs in plants, and analyse the conservation of their functions in phylogenetically distant plants. Because miRNAs are involved in most developmental and pathological processes in plants and animals, manipulating their expression with exogenously applied specific peptides could have many applications. A long term objective of this project is then to explore the agronomical and therapeutic potential of miPEPs.