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-133 [corrected] 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.
Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, et al. (2011) A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA. Cell 147: 358–369. Available: http://dx.doi.org/10.1016/j.cell.2011.09.028.
We thank N. Proudfoot and K. Perkins for introducing M. C. to the 3C analysis; M. Mora and the Telethon Neuromuscular Biobank for providing material; J. Martone, V. Cazzella for useful discussion; and M. Marchioni for technical support. D.C. is a recipient of a Microsoft research PhD fellowship. This work was partially supported by grants from: Telethon (GGP07049), Parent Project Italia, EU project SIROCCO (LSHG-CT-2006-037900), KAUST KUK-I1-012-43, AIRC, IIT "SEED," FIRB, PRIN, and BEMM.