A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA

By M. Cesana, D. Cacchiarelli, Ivano Legnini, Tiziana Santini, O. Sthandier, M. Chinappi, Anna Tramontano, I. Bozzoni. Cell, 2011

2,527 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/96d6dfc1ee549261f0c1696f110387e0aacf056a

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Citations in the corpus

In vivo identification of tumor suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma (2011, neutral): “Our findings of a microRNA-mediated andMRE-dependent gene regulatory ceRNA dimension are corroborated by two other studies demonstrating ceRNA activity for protein coding (Sumazin et al., 2011 [this issue of Cell]) and noncoding RNA (Cesana et al., 2011 [this issue of Cell]) molecules.”
On the classification of long non-coding RNAs (2013, background): “80-83 For instance, linc-MD1 (long intergenic ncRNA that is associated with muscle differentiation), a ~0.5 kb lncRNA, acts as sponge/target mimic of miR-133 and miR-135 to regulate the expression of two transcription factors: MAML1 (mastermind-like protein 1) and MEF2C (myocyte-specific enhancer…”
Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches. (2016, background): “Linc-MD1 was first described as a sponge for miR133 and miR-135, preventing these miRNAs from targeting Mef2c and Maml1, whose de-repression leads to muscle differentiation (41).”
Past, present, and future of circRNAs (2019, neutral): “…of the numbers and types of circRNA molecules in different cellular compartments. circRNA as modulators of miRNA function Some long non-coding RNAs can regulate miRNA levels and/or activity by selective sponging (Cesana et al , 2011; Tay et al , 2011; Bitetti et al , 2018; Kleaveland et al , 2018).”
Long Non-coding RNAs in the Cytoplasm (2016, background): “linc-MD1 is a muscle-specific lncRNA, which is indispensable for the timing of muscle differentiation and plays an important role in myogenesis [64].”
Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp™ (2014, background): “Recent studies have reported the potential physiological relevance of other ceRNAs, including a long noncoding RNA that regulates muscle differentiation (Cesana et al., 2011), an overexpressed 30 untranslated region (30 UTR) inducing cancer in transgenic mice (Fang et al.”
Natural RNA circles function as efficient microRNA sponges (2013, methodology): “The specificity of the signal was tested by hybridizing parallel sections with: (1) 100-fold excess of unlabelled probe, (2) pre-treatment with RNase A (Pharmacia Biotech), (3) buffer alone, or (4) Cy5-labelled miR-449 probe.”
The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease (2013, neutral): “On a related note, miRNAs were recently shown to also target intergenic and intronic regions, pseudogenes and long ncRNAs.(119,121,123,135,136) Another dimension of the miRNA target prediction problem relates to the observation of conservation of miRNA sequences across animals and plants (and viruse”
Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance. (2014, background): “studies have reported the potential physiological relevance of other ceRNAs, including a long non-coding RNA (lncRNA) regulating muscle differentiation (Cesana et al., 2011), an overexpressed 3′ untranslated region (3′UTR) inducing cancer in transgenic mice (Fang et al.”
LNCipedia: a database for annotated human lncRNA transcript sequences and structures (2012, background): “Recently, it has been shown that lncRNAs can act as a miRNA sponge by binding speciﬁc microRNAs and, thus, interfering with their role as negative regulators of gene expression (5,19,20).”