Drosophila primary microRNA-8 encodes a microRNA-encoded peptide acting in parallel of miR-8

Audrey Montigny,Patrizia Tavormina,Serge Plaza,Marielle Aguilar,Hélène San Clémente,Carine Duboe,Jean-Philippe Combier,Dominique Lauressergues,Philippe Valenti

doi:10.1186/s13059-021-02345-8

Abstract

BackgroundRecent genome-wide studies of many species reveal the existence of a myriad of RNAs differing in size, coding potential and function. Among these are the long non-coding RNAs, some of them producing functional small peptides via the translation of short ORFs. 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-miRs) 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 present in Drosophila melanogaster.ResultsWe perform a survey of ribosome profiling data and reveal that many pri-miRNAs exhibit ribosome translation marks. Focusing on miR-8, we show that pri-miR-8 can produce a miPEP-8. Functional assays performed in Drosophila reveal that miPEP-8 affects development when overexpressed or knocked down. Combining genetic and molecular approaches as well as genome-wide transcriptomic analyses, we show that miR-8 expression is independent of miPEP-8 activity and that miPEP-8 acts in parallel to miR-8 to regulate the expression of hundreds of genes.ConclusionTaken together, these results reveal that several Drosophila pri-miRs exhibit translation potential. Contrasting with the mechanism described in plants, these data shed light on the function of yet undescribed primary-microRNA-encoded peptides in Drosophila and their regulatory potential on genome expression.

Highlights

Recent genome-wide studies of many species reveal the existence of a myriad of RNAs differing in size, coding potential and function
Translation potential of short open reading frames (sORF) present in Drosophila pri-microRNAs As plants pri-miRs contain sORFs producing functional miRs encode small regulatory peptides (miPEPs) involved in a positive feedback loop on pri-miR expression (Fig. 1a), we first asked whether D. melanogaster pri-miRs contain significant levels of miORFs
Pri-miRs present the highest enrichment of sORFs/kb when compared with the 5′UTR of coding genes, sequences known to contain translatable short open reading frames, but contain similar amounts of sORFs when compared with lncRNAs, previously reported to be widely bound by ribosomes [43]

Summary

Introduction

Recent genome-wide studies of many species reveal the existence of a myriad of RNAs differing in size, coding potential and function. Among these are the long non-coding RNAs, some of them producing functional small peptides via the translation of short ORFs. It appears that any kind of RNA presumably has a potential to encode small peptides. LncRNAs control genetic information, such as chromosome structure modulation, transcription, splicing, messenger RNA (mRNA) stability, mRNA availability and post-translational modifications They act as scaffolds, bearing interaction domains for DNA, mRNAs, miRs and proteins, depending on both their primary sequence and secondary structure [3]. While lncRNAs annotated as non-coding cannot produce large-sized proteins, they all contain myriads of short open reading frames (sORF) [4,5,6,7] and a surprising result was the discovery for a subset of them of their translation into small functional peptides [8,9,10,11]

Methods

Results

Discussion

Conclusion