RNA Localization in Confined Cells Depends on Cellular Mechanical Activity and Contributes to Confined Migration

Cancer cells experience mechanical confining forces during metastasis and consequently, can alter their migratory mechanisms. Localization of numerous mRNAs to cell protrusions contributes to cell polarization and migration and is controlled by proteins that can bind RNA and/or cytoskeletal elements, such as the Adenomatous Polyposis Coli (APC). Here, we demonstrate that peripheral localization of APC-dependent RNAs in cells within confined microchannels is cell type dependent. This varying phenotype is determined by the presence or absence of a fibrillar detyrosinated tubulin network. We show that this network is regulated by mechanoactivity, and that cells with mechanosensitive ion channels and increased myosin II activity direct peripheral localization of the RAB13 APC-dependent RNA. Through specific mislocalization of the RAB13 RNA, we show that peripheral RNA localization contributes to confined cell migration. Our results indicate that a cell’s mechanical activity determines its ability to peripherally target RNAs and utilize them for movement in confinement.