Complementary peptides (cPEPs) modulate protein translation

MicroRNAs (miRNAs) are small regulatory RNAs that control plant and animal development by regulating post-transcriptional gene expression. Primary transcripts of miRNAs contain small ORFs that can be translated into small peptides (miPEPs). MiPEPs specifically enhance the expression of their cognate miRNA in a positive feedback loop. Here, by addressing the molecular bases of miPEP specificity, we identified an unanticipated mechanism modulating coding gene expression. We found that the miORF itself constitutes a prerequisite for the miPEP to specifically control the expression of its miRNA. We extended this property to any coding gene through the design of artificial peptides. We called these peptides « complementary peptides » (cPEPs) as their external application modulates the translation of their corresponding protein. We discovered here a yet undescribed mechanism of post-transcriptional regulation, opening new promising avenues in fundamental research and applied biology. Quantitative proteomics using LC-MS/MS after co-immunoprecipitation with a HA-tagged cPEP or scrambled peptide was performed to identify interactors of the cPEP or scrambled peptide in co-eluates of plants.