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Peer-reviewedCC BY 4.0Science Advances

Local translational program at the muscle-tendon junction endows domain identity in muscle syncytia

  • Nour El Khazen1,2,3,4
  • Juliana de Carvalho Neves1,2,3,4
  • Vedran Franke5
  • Coalesco Smith1,2,3,4
  • Sakulrat Mankhong1,2,3,4
  • Edgar Jauliac6
  • Laura Yedigaryan2,3,4,7
  • Elise Lefebvre2,3,4
  • Altuna Akalin5
  • Pascal Maire6
  • Minchul Kim1,2,3,4
7 affiliations
  1. 1Laboratory of Syncytial Cell Biology, IGBMC, Institute of Genetics and of Molecular and Cellular Biology, 67400 Illkirch, France.
  2. 2Université de Strasbourg, Strasbourg, France.
  3. 3CNRS, UMR 7104, 67400 Illkirch, France.
  4. 4INSERM, UMR-S 1258, 67400 Illkirch, France.
  5. 5Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Helmholtz Society, Berlin, Germany.
  6. 6Université Paris Cité, CNRS, Inserm, Institut Cochin, F-75014 Paris, France.
  7. 7Laboratory of Pathophysiology of Neuromuscular Diseases, IGBMC, Institute of Genetics and of Molecular and Cellular Biology, 67400 Illkirch, France.
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Abstract

How cells establish specialized subdomains is a fundamental question in cell and tissue biology. Skeletal muscle fibers, among the largest cells in the body, are multinucleated and form distinct regions such as the neuromuscular and myotendinous junctions (MTJs), the latter forming a critical interface between muscle and tendon that transmits contractile force. While transcriptional heterogeneity among myonuclei has been described, whether local translation contributes to domain identity remains unknown, largely due to the lack of tools for domain-specific manipulation. Here, we introduce MTJ-AAV, a viral system that enables selective genetic targeting of MTJ myonuclei. This approach allowed MTJ-specific ribosome tagging and revealed extensive translational regulation underlying MTJ biology and its remodeling during exercise. Untranslated regions of these transcripts were sufficient to control regionalized translation. Notably, the Krüpper-like factor–family transcription factors emerged as translationally up-regulated targets at the MTJ, where they drive local gene expression. Our findings establish local translation as a key layer of subcellular specialization and provide a versatile toolkit for dissecting spatial molecular regulation within muscle syncytia.

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Cite

BibTeXRIS
BibTeX
@article{khazen2026local,
  title = {{Local translational program at the muscle-tendon junction endows domain identity in muscle syncytia}},
  author = {Nour El Khazen and Juliana de Carvalho Neves and Vedran Franke and Coalesco Smith and Sakulrat Mankhong and Edgar Jauliac and Laura Yedigaryan and Elise Lefebvre and Altuna Akalin and Pascal Maire and Minchul Kim},
  journal = {Science Advances},
  year = {2026},
  month = nov,
  doi = {10.1126/sciadv.aee6166},
  url = {https://www.science.org/doi/abs/10.1126/sciadv.aee6166},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Local translational program at the muscle-tendon junction endows domain identity in muscle syncytia
AU  - Nour El Khazen
AU  - Juliana de Carvalho Neves
AU  - Vedran Franke
AU  - Coalesco Smith
AU  - Sakulrat Mankhong
AU  - Edgar Jauliac
AU  - Laura Yedigaryan
AU  - Elise Lefebvre
AU  - Altuna Akalin
AU  - Pascal Maire
AU  - Minchul Kim
PY  - 2026
DA  - 2026/11/04
JO  - Science Advances
DO  - 10.1126/sciadv.aee6166
UR  - https://www.science.org/doi/abs/10.1126/sciadv.aee6166
AB  - How cells establish specialized subdomains is a fundamental question in cell and tissue biology. Skeletal muscle fibers, among the largest cells in the body, are multinucleated and form distinct regions such as the neuromuscular and myotendinous junctions (MTJs), the latter forming a critical interface between muscle and tendon that transmits contractile force. While transcriptional heterogeneity among myonuclei has been described, whether local translation contributes to domain identity remains unknown, largely due to the lack of tools for domain-specific manipulation. Here, we introduce MTJ-AAV, a viral system that enables selective genetic targeting of MTJ myonuclei. This approach allowed MTJ-specific ribosome tagging and revealed extensive translational regulation underlying MTJ biology and its remodeling during exercise. Untranslated regions of these transcripts were sufficient to control regionalized translation. Notably, the Krüpper-like factor–family transcription factors emerged as translationally up-regulated targets at the MTJ, where they drive local gene expression. Our findings establish local translation as a key layer of subcellular specialization and provide a versatile toolkit for dissecting spatial molecular regulation within muscle syncytia.
SN  - 2375-2548
ER  -