Paraspeckle Protein NONO Promotes TAZ Phase Separation in the Nucleus to Drive the Oncogenic Transcriptional Program. Issue 24 (29th October 2021)

• Record Type: Journal Article
• Authors: Wei, Yiju; Luo, Huacheng; Yee, Patricia P.; Zhang, Lijun; Liu, Zhijun; Zheng, Haiyan; Zhang, Lei; Anderson, Benjamin; Tang, Miaolu; Huang, Suming; Li, Wei
• Is Part Of: Advanced science. Volume 8:Issue 24(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-10-29
• Subjects: glioblastoma -- Hippo pathway -- liquid–liquid phase separation -- NONO -- TAZ -- transcription regulation; Science -- Periodicals; 505
• DOI: 10.1002/advs.202102653
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: The Hippo pathway effector TAZ promotes cellular growth, survival, and stemness through regulating gene transcription. Recent studies suggest that TAZ liquid–liquid phase separation (LLPS) compartmentalizes key cofactors to activate transcription. However, how TAZ LLPS is achieved remains unknown. Here, it is shown that the paraspeckle protein NONO is required for TAZ LLPS and activation in the nucleus. NONO is a TAZ‐binding protein. Their interaction shows temporal regulation parallel to the interaction between TAZ and TEAD as well as to the expression of TAZ target genes. NONO depletion reduces nuclear TAZ LLPS, while ectopic NONO expression promotes the LLPS. Accordingly, NONO depletion reduces TAZ interactions with TEAD, Rpb1, and enhancers. In glioblastoma, expressions of NONO and TAZ are both upregulated and predict poor prognosis. Silencing NONO expression in an orthotopic glioblastoma mouse model inhibits TAZ‐driven tumorigenesis. Together, this study suggests that NONO is a nuclear factor that promotes TAZ LLPS and TAZ‐driven oncogenic transcriptional program. Abstract : The Hippo pathway effector TAZ activates transcription by compartmentalizing key cofactors through liquid–liquid phase separation (LLPS). How TAZ LLPS is achieved remains unknown. This study shows that the nuclear paraspeckle protein NONO, a TAZ‐binding protein, is required for TAZ LLPS and activation in the nucleus, as well as TAZ‐driven oncogenic transcriptional program in glioblastoma tumorigenesis.