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MTJ-AAV viral system targets myonuclei at the muscle-tendon junction and maps local translation

Authors created a viral tool for selective genetic targeting of myonuclei at the muscle-tendon junction. It showed that local translation shapes the identity of this domain in muscle fibers.

MTJ-AAV viral system targets myonuclei at the muscle-tendon junction and maps local translation
Photo: Dedebio2015, Wikimedia Commons, CC BY 4.0 · License: CC BY 4.0

A research team reported in Science Advances a viral system, MTJ-AAV, that selectively targets myonuclei at the myotendinous junction (MTJ) of skeletal muscle fibers doi.orgScience Advancesdoi.orgOpen source ↗. The MTJ is the interface between muscle and tendon that transmits contractile force. Skeletal muscle fibers are among the largest cells in the body and are multinucleated.

Transcriptional heterogeneity among myonuclei had been described earlier. Whether local translation contributes to the identity of a domain remained unknown, largely because tools for domain-specific manipulation were lacking, the authors write. With MTJ-AAV they tagged ribosomes specifically at the MTJ. This revealed extensive translational regulation underlying MTJ biology and its remodeling during exercise doi.orgScience Advancesdoi.orgOpen source ↗.

According to the authors, the untranslated regions of these transcripts were sufficient to control regionalized translation. KLF-family transcription factors emerged as translationally upregulated targets at the MTJ, where they drive local gene expression doi.orgScience Advancesdoi.orgOpen source ↗. The authors conclude that local translation is a layer of subcellular specialization, and they present the system as a toolkit for studying spatial molecular regulation within muscle syncytia.

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