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Control of epithelial tissue organization by mRNA localization

  1. Author:
    Mason, Devon E [ORCID]
    Madsen, Thomas D [ORCID]
    Gasparski, Alexander N [ORCID]
    Kong, Dong [ORCID]
    Jiwnani, Neal
    Lechler, Terry
    Loncarek,Jadranka
    Weigert, Roberto [ORCID]
    Iglesias-Bartolome, Ramiro [ORCID]
    Mili, Stavroula [ORCID]

  2. Author Address

    Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer, Institute, NIH, Bethesda, MD, USA. devon.mason@nih.gov., Cancer Innovation Laboratory, Center for Cancer Research, National Cancer institute, NIH, Frederick, MD, USA., Department of Dermatology, Duke University Medical Center, Durham, NC, USA., Department of Cell Biology, Duke University Medical Center, Durham, NC, USA., Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer, Institute, NIH, Bethesda, MD, USA. voula.mili@nih.gov.,
    1. Year: 2025
    2. Date: Jun 05
    3. Epub Date: 2025 06 05
  2. Journal: Nature Communications
    1. 16
    2. 1
    3. Pages: 5216
  4. Type of Article: Article
  5. Article Number: 5216
  1. Abstract:

    mRNA localization to specific subcellular regions is common in mammalian cells but poorly understood in terms of its physiological roles. This study demonstrates the functional importance of Net1 mRNA, which we find prominently localized at the dermal-epidermal junction (DEJ) in stratified squamous epithelia. Net1 mRNA accumulates at DEJ protrusion-like structures that interact with the basement membrane and connect to a mechanosensitive network of microfibrils. Disrupting Net1 mRNA localization in mouse epithelium alters DEJ morphology and keratinocyte-matrix connections, affecting tissue homeostasis. mRNA localization dictates the cortical accumulation of the Net1 protein and its function as a RhoA GTPase exchange factor (GEF). Altered RhoA activity is in turn sufficient to alter the ultrastructure of the DEJ. This study provides a high-resolution in vivo view of mRNA targeting in a physiological context. It further demonstrates how the subcellular localization of a single mRNA can significantly influence mammalian epithelial tissue organization, thus revealing an unappreciated level of post-transcriptional regulation that controls tissue physiology. © 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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External Sources

  1. View Full Text
  2. DOI: 10.1038/s41467-025-60532-8
  3. PMID: 40473627
  4. PMCID: PMC12141530
  5. PII : 10.1038/s41467-025-60532-8

Library Notes

  1. Fiscal Year: FY2024-2025
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