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Microtubule-based transport is essential to distribute RNA and nascent protein in skeletal muscle

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  • Lance T. Denes

    (Center for NeuroGenetics, Genetics Institute, University of Florida
    Biomedical Sciences Graduate Program, University of Florida)

  • Chase P. Kelley

    (Center for NeuroGenetics, Genetics Institute, University of Florida
    Genetics and Genomics Graduate Program, University of Florida)

  • Eric T. Wang

    (Center for NeuroGenetics, Genetics Institute, University of Florida
    Myology Institute, University of Florida)

Abstract

While the importance of RNA localization in highly differentiated cells is well appreciated, basic principles of RNA localization in skeletal muscle remain poorly characterized. Here, we develop a method to detect and quantify single molecule RNA localization patterns in skeletal myofibers, and uncover a critical role for directed transport of RNPs in muscle. We find that RNAs localize and are translated along sarcomere Z-disks, dispersing tens of microns from progenitor nuclei, regardless of encoded protein function. We find that directed transport along the lattice-like microtubule network of myofibers becomes essential to achieve this localization pattern as muscle development progresses; disruption of this network leads to extreme accumulation of RNPs and nascent protein around myonuclei. Our observations suggest that global active RNP transport may be required to distribute RNAs in highly differentiated cells and reveal fundamental mechanisms of gene regulation, with consequences for myopathies caused by perturbations to RNPs or microtubules.

Suggested Citation

  • Lance T. Denes & Chase P. Kelley & Eric T. Wang, 2021. "Microtubule-based transport is essential to distribute RNA and nascent protein in skeletal muscle," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26383-9
    DOI: 10.1038/s41467-021-26383-9
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    1. Ryan P. Hildebrandt & Kathryn R. Moss & Aleksandra Janusz-Kaminska & Luke A. Knudson & Lance T. Denes & Tanvi Saxena & Devi Prasad Boggupalli & Zhuangyue Li & Kun Lin & Gary J. Bassell & Eric T. Wang, 2023. "Muscleblind-like proteins use modular domains to localize RNAs by riding kinesins and docking to membranes," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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