@article{b31503d4e04e4939b63817ee9485ab82,
title = "Paraspeckle Protein NONO Promotes TAZ Phase Separation in the Nucleus to Drive the Oncogenic Transcriptional Program",
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.",
author = "Yiju Wei and Huacheng Luo and Yee, {Patricia P.} and Lijun Zhang and Zhijun Liu and Haiyan Zheng and Lei Zhang and Benjamin Anderson and Miaolu Tang and Suming Huang and Wei Li",
note = "Funding Information: Y.W. and H.L. contributed equally to this work. The authors would like to thank Dr. Kun‐liang Guan for reagents, members of the Li Laboratory for helpful discussions, Dr. Thomas Abraham and Wade Edris from the Microscopy Imaging Core (Leica SP8 Confocal: National Institute of Health Grant No. 1S10OD010756‐01A1 CB), Dr. Sang Lee from the Bioluminescent Imaging Core, Dr. Teodora Orendovici and Dr. Yuka Imamura from the Genomics Sciences Core, Dr. Katherine Aird from the shRNA library core, and Gretchen Snavely and Erin Mattern from the Comparative Medicine Histopathology Core. The authors acknowledge support from the National Cancer Institute (Grant No. R01 CA204044 to S.H.), National Institute of Neurological Disorders and Stroke (Grant No. R01 NS109147 to W.L.), American Cancer Society Institutional Research Grant (Grant No. 124171‐IRG‐13‐043‐01 to W.L.), and the Four Diamonds Fund for Pediatric Cancer Research (to PSU). Funding Information: Y.W. and H.L. contributed equally to this work. The authors would like to thank Dr. Kun-liang Guan for reagents, members of the Li Laboratory for helpful discussions, Dr. Thomas Abraham and Wade Edris from the Microscopy Imaging Core (Leica SP8 Confocal: National Institute of Health Grant No. 1S10OD010756-01A1 CB), Dr. Sang Lee from the Bioluminescent Imaging Core, Dr. Teodora Orendovici and Dr. Yuka Imamura from the Genomics Sciences Core, Dr. Katherine Aird from the shRNA library core, and Gretchen Snavely and Erin Mattern from the Comparative Medicine Histopathology Core. The authors acknowledge support from the National Cancer Institute (Grant No. R01 CA204044 to S.H.), National Institute of Neurological Disorders and Stroke (Grant No. R01 NS109147?to W.L.), American Cancer Society Institutional Research Grant (Grant No. 124171-IRG-13-043-01 to W.L.), and the Four Diamonds Fund for Pediatric Cancer Research (to PSU). Publisher Copyright: {\textcopyright} 2021 The Authors. Advanced Science published by Wiley-VCH GmbH",
year = "2021",
month = dec,
day = "22",
doi = "10.1002/advs.202102653",
language = "English (US)",
volume = "8",
journal = "Advanced Science",
issn = "2198-3844",
publisher = "Wiley-VCH Verlag",
number = "24",
}