RNA localization in confined cells depends on cellular mechanical activity and contributes to confined migration

Rebecca A Moriarty; Stavroula Mili; Kimberly M Stroka

doi:10.1016/j.isci.2022.103845

RNA localization in confined cells depends on cellular mechanical activity and contributes to confined migration

iScience. 2022 Feb 1;25(2):103845. doi: 10.1016/j.isci.2022.103845. eCollection 2022 Feb 18.

Authors

Rebecca A Moriarty^{1

2}, Stavroula Mili¹, Kimberly M Stroka^{2

3

4

5}

Affiliations

¹ Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
² Fischell Department of Bioengineering, University of Maryland College Park, College Park, MD 20742, USA.
³ Maryland Biophysics Program, University of Maryland College Park, College Park, MD 20742, USA.
⁴ Center for Stem Cell Biology & Regenerative Medicine, University of Maryland Baltimore, Baltimore, MD 21202, USA.
⁵ Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Baltimore, Baltimore, MD 21202, USA.

Abstract

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 levels of a 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.

Keywords: Bioengineering; Biological sciences; Biophysics; Cell biology.