Epithelial Cell Transforming 2 and Aurora Kinase B Modulate Formation of Stress Granule-Containing Transcripts from Diverse Cellular Pathways in Astrocytoma Cells.
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 epithelial cell transforming 2 and Aurora kinase B (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 using 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 harbor unique mRNAs for various cellular pathways, including cellular migration, metabolism, translation, and transcriptional regulation. Human astrocytoma cell stress granules contain mRNAs that are known to be involved in glioma signaling and the mammalian target of rapamycin 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 susceptibility to conventional therapy, such as radiation and chemotherapy.
Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada; Division of Neurosurgery, Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada.
Adrienne
A
Weeks
Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada.
Sameer
S
Agnihotri
Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada.
Jennifer
J
Lymer
Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada.
Alan
A
Chalil
Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada.
Roberto
R
Diaz
Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada.
Semra
S
Isik
Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada.
Christian
C
Smith
Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Toronto, Ontario, Canada. Electronic address: james.rutka@sickkids.ca.
James T
JT
Rutka
D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology*; D064107:Aurora Kinase B / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D002352:Carrier Proteins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D004265:DNA Helicases; D044127:Epigenesis, Genetic; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D053208:Kaplan-Meier Estimate; D020411:Oligonucleotide Array Sequence Analysis; D000075223:Poly-ADP-Ribose Binding Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis; D013312:Stress, Physiological / Q000502:physiology*; D014162:Transfection
D015415:Biomarkers; D002352:Carrier Proteins; C489850:ECT2 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D011518:Proto-Oncogene Proteins; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C076751:TIAL1 protein, human; C576921:AURKB protein, human; D064107:Aurora Kinase B; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases