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Article Dans Une Revue International Journal of Molecular Sciences Année : 2022

Small ORFs as New Regulators of Pri-miRNAs and miRNAs Expression in Human and Drosophila

Résumé

MicroRNAs (miRNAs) are small regulatory non-coding RNAs, resulting from the cleavage of long primary transcripts (pri-miRNAs) in the nucleus by the Microprocessor complex generating precursors (pre-miRNAs) that are then exported to the cytoplasm and processed into mature miRNAs. Some miRNAs are hosted in pri-miRNAs annotated as long non-coding RNAs (lncRNAs) and defined as MIRHGs (for miRNA Host Genes). However, several lnc pri-miRNAs contain translatable small open reading frames (smORFs). If smORFs present within lncRNAs can encode functional small peptides, they can also constitute cis-regulatory elements involved in lncRNA decay. Here, we investigated the possible involvement of smORFs in the regulation of lnc pri-miRNAs in Human and Drosophila, focusing on pri-miRNAs previously shown to contain translatable smORFs. We show that smORFs regulate the expression levels of human pri-miR-155 and pri-miR-497, and Drosophila pri-miR-8 and pri-miR-14, and also affect the expression and activity of their associated miRNAs. This smORF-dependent regulation is independent of the nucleotidic and amino acidic sequences of the smORFs and is sensitive to the ribosome-stalling drug cycloheximide, suggesting the involvement of translational events. This study identifies smORFs as new cis-acting elements involved in the regulation of pri-miRNAs and miRNAs expression, in both Human and Drosophila melanogaster.

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hal-03676309 , version 1 (24-05-2022)

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Christine Dozier, Audrey Montigny, Mireia Viladrich, Raphael Culerrier, Jean-Philippe Combier, et al.. Small ORFs as New Regulators of Pri-miRNAs and miRNAs Expression in Human and Drosophila. International Journal of Molecular Sciences, 2022, 23 (10), pp.5764. ⟨10.3390/ijms23105764⟩. ⟨hal-03676309⟩
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