Control of Epithelial Tissue Organization by mRNA Localization.

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 mRNA, which we find prominently localized at the dermal-epidermal junction (DEJ) in stratified squamous epithelia. mRNA accumulates at DEJ protrusion-like structures that interact with the basement membrane and connect to a mechanosensitive network of microfibrils. Disrupting 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 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.