Micro-ARNs et différenciation musculaire

Micro-RNAs and muscle differentiation

CNRS FRE 2944 "Épigénétique et Cancer", Institut André Lwoff, 7 rue Guy Môquet, BP8, 94801 VILLEJUIF Cedex, France. Adresse actuelle LSHL-SDV / IRCM-CEA 18 route du Panorama, BP6, 92265 Fontenay-aux-Roses

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Reçu : 23 Janvier 2007

Résumé

Les micro-ARNs endogènes représentent une fraction très importante des ARNs non codants qui répriment l'expression des gènes au niveau post-transcriptionnel. Parmi ces micro-ARNs se trouve le miR-181a. Il intervient dans les processus de différenciation et de régénération des muscles squelettiques en réprimant les gènes qui bloquent la différenciation, notamment la protéine Hox-A11.

Abstract

Deciphering the mechanisms underlying skeletal muscle differentiation in mammals is an important challenge. Cell differentiation involves complex pathways regulated at both transcriptional and post-transcriptional levels. Recent observations have revealed the importance of small (20–25 base pairs) non-coding RNAs (microRNAs or miRNAs) that are expressed in both lower organisms and in mammals. miRNAs modulate gene expression by affecting mRNA translation or stability. In lower organisms, miRNAs are essential for cell differentiation during development; some miRNAs are involved in maintenance of the differentiated state. We have shown that miR-181, a microRNA that is strongly upregulated during differentiation, participates in establishing the muscle phenotype. Moreover, our results suggest that miR-181 downregulates the homeobox protein Hox-A11 (a repressor of the differentiation process), thus establishing a functional link between miR-181 and the complex process of mammalian skeletal muscle differentiation. Therefore, miRNAs can be involved in the establishment of a differentiated phenotype – even when they are not expressed in the corresponding fully differentiated tissue.