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bioRxiv · 10.1101/2024.12.02.626432

Control of Epithelial Tissue Organization by mRNA Localization

Mason, D. E.·Madsen, T. D.·Gasparski, A. N.·Jiwnani, N.·Lechler, T.·Weigert, R.·Iglesias-Bartolome, R.·Mili, S.
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Abstract

mRNA localization to specific subcellular regions is common in mammalian cells but poorly understood in terms of its physiological roles1-6,7. 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 Net1 protein distribution 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.

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Mason, D. E., Madsen, T. D., Gasparski, A. N., Jiwnani, N., Lechler, T., Weigert, R., Iglesias-Bartolome, R., Mili, S.. 2024-12-02. Control of Epithelial Tissue Organization by mRNA Localization. https://doi.org/10.1101/2024.12.02.626432

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