Paraspeckle Protein NONO Promotes TAZ Phase Separation in the Nucleus to Drive the Oncogenic Transcriptional Program

Yiju Wei, Huacheng Luo, Patricia P. Yee, Lijun Zhang, Zhijun Liu, Haiyan Zheng, Lei Zhang, Benjamin Anderson, Miaolu Tang, Suming Huang, Wei Li

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number2102653
JournalAdvanced Science
Volume8
Issue number24
DOIs
StatePublished - Dec 22 2021

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Materials Science(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Engineering(all)
  • Physics and Astronomy(all)

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