Morphoregulatory functions of the RNA-binding motif protein 3 in cell spreading, polarity and migration

Abstract

RNA-binding proteins are emerging as key regulators of transitions in cell morphology. The RNA-binding motif protein 3 (RBM3) is a cold-inducible RNA-binding protein with broadly relevant roles in cellular protection, and putative functions in cancer and development. Several findings suggest that RBM3 has morphoregulatory functions germane to its roles in these contexts. For example, RBM3 helps maintain the morphological integrity of cell protrusions during cell stress and disease. Moreover, it is highly expressed in migrating neurons of the developing brain and in cancer invadopodia, suggesting roles in migration. We here show that RBM3 regulates cell polarity, spreading and migration. RBM3 was present in spreading initiation centers, filopodia and blebs that formed during cell spreading in cell lines and primary myoblasts. Reducing RBM3 triggered exaggerated spreading, increased RhoA expression, and a loss of polarity that was rescued by Rho kinase inhibition and overexpression of CRMP2. High RBM3 expression enhanced the motility of cells migrating by a mesenchymal mode involving extension of long protrusions, whereas RBM3 knockdown slowed migration, greatly reducing the ability of cells to extend protrusions and impairing multiple processes that require directional migration. These data establish novel functions of RBM3 of potential significance to tissue repair, metastasis and development.

An IKK/NF-κB Activation/p53 Deletion Sequence Drives Liver Carcinogenesis and Tumor Differentiation

“…Higher Rbm3 expression was confirmed by qPCR, western blot analysis and immunohistochemistry (Figure 6B–E and Figure S13). RBM3 has been reported to be involved in carcinogenesis [28,29]. Data from the TIGER-LC and TCGA showed a similar expression pattern for Rbm3 in adjacent human liver, HCC and ICC samples, respectively, when compared to our murine data (Figure 6F,G).…”

“…Rbm3 was also upregulated in two independent cohorts of human liver carcinomas, especially in ICCs. RBM3 has been reported to promote the development of colitis-associated cancer or enhance migration ability in neuroblastoma cell lines [28,29]. In addition, high RBM3 levels were significantly associated with reduced overall survival in pancreatic cancer [39].…”

Molecular characterization of triple negative breast cancer formaldehyde-fixed paraffin-embedded samples by data-independent acquisition proteomics

“…RBM3 is a member of the cold-shock protein family that regulates mRNA metabolism and has pleiotropic effects in cellular stress and oncogenesis (46). RBM3 protein is rarely overexpressed in normal tissues, but it is overexpressed in some solid tumors and, in recent studies, its expression levels seem to be related to prognosis and cytostatic sensitivity.…”

TrkB signaling regulates the cold-shock protein RBM3-mediated neuroprotection

“…Others have shown that RBM3 mediates the protective effects of hypothermia in brain slices ( Chip et al, 2011 ). Furthermore, RBM3 is known to increase global protein synthesis rates ( Dresios et al, 2004 ), particularly in dendrites ( Smart et al, 2007 ) and to regulate neuronal polarity ( Pilotte et al, 2018 ) and neurogenesis during development ( Xia et al, 2018 ), which may contribute to its effects on structural plasticity.…”