Paraspeckle Protein NONO Promotes TAZ Phase Separation in the Nucleus to Drive the Oncogenic Transcriptional Program.
Paraspeckle Protein NONO Promotes TAZ Phase Separation in the Nucleus to Drive the Oncogenic Transcriptional Program.
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DOI：
10.1002/advs.202102653
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Wei Y;Luo H;Yee PP;Zhang L;Liu Z;Zheng H;Zhang L;Anderson B;Tang M;Huang S;Li W
河马途径效应器TAZ通过调节基因转录促进细胞生长、存活和茎的形成。最近的研究表明，TAZ液-液相分离(LLP)将激活转录的关键辅助因子区分开来。然而，TAZ LLP是如何实现的仍是个未知数。这里，它表明了副斑点蛋白NONO是TAZ LLP和细胞核激活所必需的。NONO是一种TAZ结合蛋白。它们的相互作用表现出与TAZ和TEAD之间的相互作用以及TAZ靶基因的表达平行的时间调节。NONO耗竭减少核TAZ LLPs，而异位NONO表达促进LLPs。因此，NONO的耗竭减少了TAZ与TEAD、Rpb1和增强剂的相互作用。在胶质母细胞瘤中，NONO和TAZ的表达均上调，预后不良。沉默原位胶质母细胞瘤小鼠模型中NONO的表达可抑制TAZ驱动的肿瘤发生。综上所述，这项研究表明，NONO是一个促进TAZ LLP和TAZ驱动的致癌转录程序的核因子。河马途径效应器TAZ通过液-液相分离(LLP)将关键的辅因子区隔，从而激活转录。TAZ有限合伙人是如何实现的，目前尚不清楚。这项研究表明，核旁斑蛋白NONO，一种TAZ结合蛋白，是TAZ LLPs和核内激活所必需的，以及在胶质母细胞瘤发生中TAZ驱动的致癌转录程序。
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. 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.
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影响因子：
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DOI：
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