A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA.

Marcella Cesana, Davide Cacchiarelli, Ivano Legnini, Tiziana Santini, Olga Sthandier, Mauro Chinappi, Anna Tramontano, Irene Bozzoni

Research output: Contribution to journalArticlepeer-review

2199 Scopus citations


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.
Original languageEnglish (US)
Pages (from-to)358-369
Number of pages12
Issue number2
StatePublished - Oct 17 2011
Externally publishedYes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): KUK-I1-012-43
Acknowledgements: 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.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.


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