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Closed form of ezrin binds RNA to maintain a metastatic phenotype in osteosarcoma

ABSTRACT: Ezrin is a cytoplasmic protein that can exist in multiple conformational forms that are regulated by phosphorylation at the threonine 567 residue. Phosphorylated open form of ezrin was generally accepted as the active form because it can translocate to the plasma membrane whereas unphosphorylated closed ezrin, sequestered in the cytoplasm, have been considered inactive. Here, we identified closed ezrin as a novel RNA binding protein with biological activity. Our previous work established that ezrin directly interacts with cytoplasmic RNA binding proteins (RBPs). Here we show that ezrin expression correlates with RBPs in human osteosarcoma samples. Recombinant ezrin in its closed conformation directly bound RNA with 6.1 nM affinity. Ezrin binding specificity was highest for the guanine-rich sequences and RNA G-quadruplexes (G4 RNA). Reintroduction of closed ezrin expression rescued the transcriptome and proteome profiles in an ezrin-null osteosarcoma cell line. Closed ezrin also bound endogenous mRNAs that were enriched for pathways related to RNA processing and splicing, DNA maintenance, and cellular metabolism. Closed ezrin also rescued the metastatic capability of osteosarcoma xenografts in zebrafish. Taken together, our data established that the closed conformation of ezrin, previously thought to be inactive, can directly bind RNA and contribute to the metastatic phenotype.

ORGANISM(S): Mus musculus

PROVIDER: GSE309914 | GEO | 2026/03/19

REPOSITORIES: GEO

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