Control of epithelial tissue organization by mRNA localization

Devon E. Mason (), Thomas D. Madsen, Alexander N. Gasparski, Dong Kong, Neal Jiwnani, Terry Lechler, Jadranka Loncarek, Roberto Weigert, Ramiro Iglesias-Bartolome and Stavroula Mili ()
Additional contact information
Devon E. Mason: NIH
Thomas D. Madsen: NIH
Alexander N. Gasparski: NIH
Dong Kong: NIH
Neal Jiwnani: NIH
Terry Lechler: Duke University Medical Center
Jadranka Loncarek: NIH
Roberto Weigert: NIH
Ramiro Iglesias-Bartolome: NIH
Stavroula Mili: NIH

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60532-8

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