Drosophilaprimary microRNA-8 encodes a microRNA encoded peptide acting in parallel ofmiR-8

Abstract

Background: In the last decades, genome-wide studies of many species have revealed the existence of a myriad of RNAs differing in size, coding potential and function. Among these are the long non-coding RNAs (lncRNAs), some of them producing functional small peptides via the translation of short ORFs (sORFs). It now appears that any kind of RNA presumably has a potential to encode small peptides. Accordingly, our team recently discovered that plant primary transcripts of microRNAs (pri-miRNAs) produce small regulatory peptides (miPEPs) involved in auto-regulatory feedback loops enhancing their cognate microRNA expression which in turn controls plant development. Here we investigate whether this regulatory feedback loop is conserved in Drosophila melanogaster. Results: We performed a survey of ribosome profiling data and revealed that many pri-miRNAs exhibit ribosome translation marks. Focusing on miR-8, we showed that pri-miR-8 can produce a miPEP-8. Functional assays performed in Drosophila revealed that miPEP-8 affects development when over-expressed or knocked down. Combining genetic and molecular approaches as well as genome-wide transcriptomic analyses, we showed that miR-8 expression is independent of miPEP-8 activity and that miPEP-8 acts in parallel of miR-8 to regulate the expression of hundreds of genes. Conclusion: Taken together, these results reveal that several Drosophila pri-miRNAs exhibit translation potential. Contrasting with the mechanism described in plants, these data shed light on the function of yet un-described microRNA encoded peptides in Drosophila and their regulatory potential on genome expression.

Characterization of plant microRNA-encoded peptides (miPEPs) reveals molecular mechanisms from the translation to activity and specificity

“…Until now, miPEPs have been shown to be encoded by the first open reading frame (miORF) after the transcription start site (TSS) located in the 5 0 region of the pri-miRNA and they enhance pri-miRNA transcription from which they originate (Lauressergues et al, 2015;Sharma et al, 2020;Chen et al, 2020). Initially characterized in Arabidopsis thaliana, Medicago truncatula, and Glycine max (Lauressergues et al, 2015;Couzigou et al, 2016Couzigou et al, , 2017, recent studies revealed the presence of miPEPs in other plant species (Chen et al, 2020;Zhang et al, 2020;Ormancey et al, 2021) and even in animals (Kang et al, 2020;Niu et al, 2020;Prel et al, 2021;Montigny et al, 2021;Immarigeon et al, 2021). This suggests that the number of miPEPs is probably far to be fully determined, and that miPEPs might be a common feature in both plant and animal kingdoms.…”