A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA
Open accessAbstract
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.
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lncRNAs act as competing endogenous RNAs (ceRNAs) by competing for binding to miRNAs.
“increasing experimental evidence has confirmed that lncRNAs act as competing endogenous RNAs (ceRNAs) by competing for binding to miRNAs”
From Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway (2017) · cites this paper as [16]
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- Authors
- Cesana, M., Cacchiarelli, D., Legnini, I., Santini, T., Sthandier, O., Chinappi, M., Tramontano, A., & Bozzoni, I.
- Affiliations
- Sapienza University of Rome (IT)
- Italian Institute of Technology (IT)
- Corresponding author
- Bozzoni, Irene
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 147
- Issue
- 2
- Pages
- 358-369
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3234495
- OpenAlex
- W2145931730
- Cited by
- 2,554
- References
- 3
- Citations by year
- 2026: 55 · 2025: 57 · 2024: 116 · 2023: 98 · 2022: 165 · 2021: 231 · 2020: 268 · 2019: 266 · 2018: 235 · 2017: 257 · 2016: 179 · 2015: 210 · 2014: 179 · 2013: 140 · 2012: 86
- FWCI
- 45.06
- Type
- journal article
- Language
- en
- Update notices
- erratum (2011-11-11)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- King Abdullah University of Science and Technology Repository (King Abdullah University of Science and Technology) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- long non-coding RNA, competing endogenous RNA, myogenesis, miR-133, microRNA sponge, MAML1, MEF2C, myoblasts, Duchenne muscular dystrophy, post-transcriptional regulation
- MeSH terms
- Animals, Base Sequence, DNA-Binding Proteins, Humans, Molecular Sequence Data, Nuclear Proteins, RNA Processing, Post-Transcriptional, Transcription Factors, Myogenic Regulatory Factors, Muscle, Skeletal, Gene Expression Regulation, Developmental, Muscular Dystrophy, Duchenne, RNA, Untranslated, Muscle Development, MADS Domain Proteins, Myoblasts, MicroRNAs, Mice, RNA, Long Noncoding, MEF2 Transcription Factors
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