Cell
Volume 147, Issue 2, 14 October 2011, Pages 358-369
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Article
A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA

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Summary

Recently, a new regulatory circuitry has been identified in which RNAs can crosstalk with each other by competing for shared microRNAs. Such competing endogenous RNAs (ceRNAs) regulate the distribution of miRNA molecules on their targets and thereby impose an additional level of post-transcriptional regulation. Here we identify a muscle-specific long noncoding RNA, linc-MD1, which governs the time of muscle differentiation by acting as a ceRNA in mouse and human myoblasts. Downregulation or overexpression of linc-MD1 correlate with retardation or anticipation of the muscle differentiation program, respectively. We show that linc-MD1 “sponges” miR-133 and miR-135 to regulate the expression of MAML1 and MEF2C, transcription factors that activate muscle-specific gene expression. Finally, we demonstrate that linc-MD1 exerts the same control over differentiation timing in human myoblasts, and that its levels are strongly reduced in Duchenne muscle cells. We conclude that the ceRNA network plays an important role in muscle differentiation.

Highlights

► linc-MD1 is a long noncoding cytoplasmic RNA expressed during myoblast differentiation ► linc-MD1 acts as a competitive endogenous RNA (ceRNA) for miR-133 and miR-135 targets ► Through these miRNAs, linc-MD1 controls MEF2C and MAML1 and myoblast differentiation ► linc-MD1 is conserved in humans and levels are reduced in Duchenne Muscular Dystrophy

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These authors contributed equally to the work