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bioRxiv · 10.1101/2021.03.22.434418

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

Montigny, A.·Tavormina, P.·Duboe, C.·San Clemente, H.·Aguilar, M.·Valenti, P.·Lauressergues, D.·Combier, J. P.·Plaza, S.
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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-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 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-miRNAs exhibit translation potential. Contrasting with the mechanism described in plants, these data shed light on the function of yet un-described pri-microRNA encoded peptides in Drosophila and their regulatory potential on genome expression.

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Montigny, A., Tavormina, P., Duboe, C., San Clemente, H., Aguilar, M., Valenti, P., Lauressergues, D., Combier, J. P., Plaza, S.. 2021-03-22. Drosophila primary microRNA-8 encodes a microRNA encoded peptide (miPEP) acting in parallel of miR-8. https://doi.org/10.1101/2021.03.22.434418

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