Compartmentalization of mRNA and Translation by Desmosomes

Subcellular compartmentalization enables cells to concentrate and locally regulate functions. Here we find that translational machinery is compartmentalized to the cell cortex in epidermal cells. Furthermore, we observed broad enrichment of transcripts at the cortex, establishing a novel axis of mRNA organization in these cells. Mechanistically, we identified the desmosomal protein, desmoplakin, to be essential for cortical recruitment of both ribosomes and mRNAs, through distinct mechanisms. While mRNA localization is usually proposed to promote local translation, we found that most cortical transcripts were translationally repressed. These findings reveal spatial and transcript-dependent features of the cortical translatome. One mediator of this regulation is the RNA-induced Silencing Complex (RISC) which is also cortically enriched in a desmoplakin-dependent manner. Under homeostatic conditions, cortical RISC associates with transcripts for cell adhesion and the cytoskeleton. Upon wounding RISC is delocalized from the cortex and its associated transcripts become translationally upregulated. Together our data demonstrate a desmosome-dependent cortical compartmentalization of translation that dynamically responds to barrier perturbations, including wounding.