Naguibneva Irina, Polesskaya Anna, Ameyar-Zazoua Maya, Souidi Mouloud, Groisman Reguina, Cuvellier Sylvain, Ait-Si-Ali Slimane, Pritchard Linda L, Harel-Bellan Annick
CNRS FRE 2944 Epigénétique et Cancer, Institut André Lwoff, 7 rue Guy Môquet, BP8, 94801 Villejuif Cedex, France.
J Soc Biol. 2007;201(4):367-76. doi: 10.1051/jbio:2007902. Epub 2008 Mar 5.
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.
解析哺乳动物骨骼肌分化的潜在机制是一项重大挑战。细胞分化涉及在转录和转录后水平调控的复杂途径。最近的观察结果揭示了小型(20 - 25个碱基对)非编码RNA(微小RNA或miRNA)的重要性,这些RNA在低等生物和哺乳动物中均有表达。miRNA通过影响mRNA的翻译或稳定性来调节基因表达。在低等生物中,miRNA对于发育过程中的细胞分化至关重要;一些miRNA参与维持分化状态。我们已经表明,miR - 181是一种在分化过程中强烈上调的微小RNA,它参与建立肌肉表型。此外,我们的结果表明,miR - 181下调同源盒蛋白Hox - A11(分化过程的一种抑制因子),从而在miR - 181与哺乳动物骨骼肌分化的复杂过程之间建立了功能联系。因此,即使miRNA在相应的完全分化组织中不表达,它们也可能参与分化表型的建立。