Long Non-Coding RNA Myoparr Regulates GDF5 Expression in Denervated Mouse Skeletal Muscle
Open accessAbstract
Skeletal muscle is a highly plastic tissue and decreased skeletal muscle mass (muscle atrophy) results in deteriorated motor function and perturbed body homeostasis. Myogenin promoter-associated long non-coding RNA (lncRNA) Myoparr promotes skeletal muscle atrophy caused by surgical denervation; however, the precise molecular mechanism remains unclear. Here, we examined the downstream genes of Myoparr during muscle atrophy following denervation of tibialis anterior (TA) muscles in C57BL/6J mice. Myoparr knockdown affected the expression of 848 genes. Sixty-five of the genes differentially regulated by Myoparr knockdown coded secretory proteins. Among these 65 genes identified in Myoparr-depleted skeletal muscles after denervation, we focused on the increased expression of growth/differentiation factor 5 (GDF5), an inhibitor of muscle atrophy. Myoparr knockdown led to activated bone morphogenetic protein (BMP) signaling in denervated muscles, as indicated by the increased levels of phosphorylated Smad1/5/8. Our detailed evaluation of downstream genes of Myoparr also revealed that Myoparr regulated differential gene expression between myogenic differentiation and muscle atrophy. This is the first report demonstrating the in vivo role of Myoparr in regulating BMP signaling in denervated muscles. Therefore, lncRNAs that have inhibitory activity on BMP signaling may be putative therapeutic targets for skeletal muscle atrophy.
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Specific lncRNAs such as Myoparr act as promoters of cellular growth and myogenic activity, physically interacting with transcription factors to drive adaptation primarily during in vitro myogenic differentiation.
“Meanwhile, specific lncRNAs (such as Myoparr) act as crucial promoters of cellular growth and myogenic activity, physically interacting with transcription factors to drive adaptation primarily during in vitro myogenic differentiation [195].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [195]
The Introduction says Myoparr promotes myogenic differentiation, and the Discussion says it binds Ddx17, a transcriptional co-activator of MyoD, during differentiation (page numbers unavailable). But the paper does not describe Myoparr as promoting cellular growth: its Results report that Myoparr knockdown preserves muscle mass after denervation. The paper also studies this in vivo role, rather than presenting Myoparr’s activity as primarily an in vitro adaptation. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSeveral classes of non-coding RNAs, including lncRNAs, miRNAs, and snoRNAs, participate in the control of nucleolar activity and ribosome production.
“Increasing evidence indicates that several classes of non-coding RNAs, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small nucleolar RNAs (snoRNAs), participate in the control of nucleolar activity and ribosome production [194,195].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [195]
The Introduction describes broad regulatory roles for lncRNAs, but does not connect them to nucleolar activity or ribosome production. Searches for those processes and for snoRNAs and miRNAs found no passage in our copy addressing the attributed claim. (LLM, conf=0.77)
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Muñoz López, M., López-Gil, J. F., Ramírez de la piscina Viúdez, X., Baz-Valle, E., & Tornero Aguilera, J. F. (2026) · Cells · doi:10.3390/cells15111041 · Cited by 1 · see citing works
“Non-coding RNAs lncRNAs, miRNAs, and snoRNAs Contribute to the regulation of myogenic transcription, RNA stability, and pre-rRNA processing, thereby potentially influencing ribosome biogenesis at multiple levels [195,198].”
- Authors
- Hitachi, K., Nakatani, M., & Tsuchida, K.
- Affiliations
- Fujita Health University (JP)
- Corresponding author
- Tsuchida, Kunihiro
- Venue
- Non-Coding RNA
- Publisher
- MDPI AG
- Published
- 2019-04-08
- Volume
- 5
- Issue
- 2
- Pages
- 33
- ISSN
- 2311-553X (ISSN-L)
- PMC
- PMC6631233
- OpenAlex
- W2937552957
- Cited by
- 19
- References
- 55
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 2
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Non-Coding RNA (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Society for the Promotion of Science (16K08599, 17K08646)
- Nakatomi Foundation (2017)
- NCNP (Intramural Research Grant (29-4) for Neurological and Psychiatric Disorders)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Keywords
- long non-coding RNA, GDF5, skeletal muscle atrophy, denervation, BMP signaling, Smad1/5/8 phosphorylation, tibialis anterior, myogenesis, secreted proteins, muscle plasticity, therapeutic target
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