title: Depletion of RNA-binding protein RBM8A (Y14) causes cell cycle deficiency and apoptosis in human cells.
abstract: RBM8A (Y14) contains an RNA-binding motif and forms a tight heterodimer with Magoh. The heterodimer is known to be a member of the exon junction complex that forms on mRNA before export and it is required for mRNA metabolism processes such as splicing, mRNA export and nonsense-mediated mRNA decay. Recently, deficient cellular proliferation has been observed in RBM8A- or Magoh-depleted cells. These results prompted us to study the role of RBM8A in cell cycle progression of human tumour cells. The depletion of RBM8A in A549 cells resulted in poor cell survival and the accumulation of mitotic cells. After release from G1/S arrest induced by a double thymidine block, the RBM8A-silenced cells could not proceed to the next G1 phase beyond G2/M phase. Finally, the sub-G1 population increased and the apoptosis markers caspases 3/7 were activated. Silenced cells exhibited an increased frequency of multipolar or monopolar centrosomes, which may have caused the observed deficiency in cell cycle progression. Finally, silencing of either RBM8A or Magoh resulted in mutual downregulation of the other protein. These results illustrate that the RBM8A-Magoh mRNA binding complex is required for M phase progression and both proteins may be novel targets for anticancer therapy.
authors: Division of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Uchinada-machi, Kahoku-gun 920-0293, Japan.
authors: Yasuhito
authors: Y
authors: Ishigaki
authors: Yuka
authors: Y
authors: Nakamura
authors: Takanori
authors: T
authors: Tatsuno
authors: Mitsumasa
authors: M
authors: Hashimoto
authors: Takeo
authors: T
authors: Shimasaki
authors: Kuniyoshi
authors: K
authors: Iwabuchi
authors: Naohisa
authors: N
authors: Tomosugi
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D020169:Caspases / Q000235:genetics / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018385:Centrosome / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D016193:G1 Phase / Q000235:genetics / Q000502:physiology; D020868:Gene Silencing / Q000187:drug effects; D006367:HeLa Cells / Q000473:pathology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*
chemical_list: C491494:MAGOH protein, human; D009687:Nuclear Proteins; C406243:RBM8A protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D020169:Caspases
keywords: G2/M phase; Magoh; RBM8A (Y14); apoptosis; cell cycle