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The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation


Deciphering the mechanisms underlying skeletal muscle-cell 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 pair) non-coding RNAs (microRNAs or miRNAs) that are expressed in both lower organisms1 and in mammals2,3. miRNAs modulate gene expression by affecting mRNA translation4 or stability5. In lower organisms, miRNAs are essential for cell differentiation during development6,7,8,9; some miRNAs are involved in maintenance of the differentiated state. Here, we show 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.

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Figure 1: miR-181 is expressed in muscle.
Figure 2: Inhibition of miR-181 affects myoblast differentiation.
Figure 3: Hox-A11 expression pattern in muscle.
Figure 4: Hox-A11 is a target for miR-181.
Figure 5: miR-181 pathway in terminally differentiating myoblasts.

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We are grateful to S. Shiaffino and to Ambion for useful technical advices; to S. Kaupinen (Exiqon), K. Arar, A. Chauchereau and M. Gerard for the kind gift of reagents, and to L. L. Pritchard, A. Hamiche and J. B. Weitzman for critical reading of the manuscript. This work was supported by the Ligue contre le Cancer and the European Union's 6th Framework Program (grant number LSHB-CT-2004-005276).

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Correspondence to Annick Harel-Bellan.

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Supplementary figures S1, S2a to S2c and S3a to S3d (PDF 105 kb)

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Naguibneva, I., Ameyar-Zazoua, M., Polesskaya, A. et al. The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation. Nat Cell Biol 8, 278–284 (2006).

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