ECT2 and AURKB Modulate Formation of Stress Granules Containing Transcripts from Diverse Cellular Pathways in Astrocytoma Cells

ABSTRACT: Stress granules are small RNA-protein granules that modify the translational landscape during cellular stress to promote survival. The RhoGTPase RhoA is implicated in the formation of RNA stress granules. Our data demonstrate that the cytokinetic proteins ECT2 and AurkB are localized to stress granules in human astrocytoma cells. AurkB and its downstream target histone-3 are phosphorylated during arsenite-induced stress. Chemical (AZD1152-HQPA) and siRNA inhibition of AurkB results in fewer and smaller stress granules when analyzed utilizing high throughput fluorescent based cellomics assays. RNA immunoprecipitation with the known stress granule aggregates TIAR and G3BP1 was performed on astrocytoma cells and subsequent analysis revealed that astrocytoma stress granules harbour unique mRNAs for various cellular pathways including cellular migration, metabolism, translation and transcriptional regulation. Human astrocytoma cell stress granules contain mRNA that are known to be involved in glioma signaling and the mTOR pathway. These data provide evidence that RNA stress granules are a novel form of epigenetic regulation in astrocytoma cells, which may be targetable by chemical inhibitors and enhance astrocytoma susceptiblity to conventional therapy such as radiation and chemotherapy. Astrocytoma cells were either untreated or treated with arsenite to induce stress granule formation and RNA immunoprecipitates were analyzed by exon array analysis. RNA species that were enriched in TIAR RIPs and G3BP1 RIPS, respectively were compared to compared to TIAR and G3BP1 RIPs from untreated cells and input controls. Ingenuity pathway analysis was performed on the stress granule enriched mRNAs from the TIAR and G3BP1 RIPs to identify significant functional biology networks.

ORGANISM(S): Homo sapiens

SUBMITTER: James Rutka 

PROVIDER: E-GEOD-76814 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress