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journal article·2021-12Open access

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

Advanced Science· Volume 8· Issue 24
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Source abstract

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.
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Research context

OpenAlex topics: Hippo pathway signaling and YAP/TAZ · RNA Research and Splicing · Cellular Mechanics and Interactions

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Division of Pediatric Hematology and Oncology Department of Pediatrics Penn State Health Hershey Medical Center Penn State College of Medicine Hershey PA 17033 USA

Department of Pharmacology Penn State Health Hershey Medical Center Penn State College of Medicine Hershey PA 17033 USA

Institute for Personalized Medicine Penn State Health Hershey Medical Center Penn State College of Medicine Hershey PA 17033 USA

Department of Biochemistry & Molecular Biology Penn State Health Hershey Medical Center Penn State College of Medicine Hershey PA 17033 USA

Biological Mass Spectrometry Facility Robert Wood Johnson Medical School, Rutgers The State University of New Jersey Piscataway NJ 08854 USA

Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei Province 430030 China

Penn State Cancer Institute Penn State Health Hershey Medical Center Penn State College of Medicine Hershey PA 17033 USA

Funding

National Cancer Institute · National Institute of Neurological Disorders and Stroke

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