A chaperone-like function of FUS ensures TAZ condensate dynamics and transcriptional activation
Shao, Yangqing Shu, Xin Lu, Yi Zhu, Wenxuan Li, Ran Fu, Huanyi Li, Chengyu Sun, Wei Li, Zhuo Zhang, Yitong
Shao, Yangqing
Shu, Xin
Lu, Yi
Zhu, Wenxuan
Li, Ran
Fu, Huanyi
Li, Chengyu
Sun, Wei
Li, Zhuo
Zhang, Yitong
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2024-01
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Article
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Cell signaling,Chemical biology,Transcription
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Shao, Y., Shu, X., Lu, Y. et al. A chaperone-like function of FUS ensures TAZ condensate dynamics and transcriptional activation. Nat Cell Biol 26, 86-99 (2024). https://doi.org/10.1038/s41556-023-01309-3
Abstract
The Hippo pathway has important roles in organ development, tissue homeostasis and tumour growth. Its downstream effector TAZ is a transcriptional coactivator that promotes target gene expression through the formation of biomolecular condensates. However, the mechanisms that regulate the biophysical properties of TAZ condensates to enable Hippo signalling are not well understood. Here using chemical crosslinking combined with an unbiased proteomics approach, we show that FUS associates with TAZ condensates and exerts a chaperone-like effect to maintain their proper liquidity and robust transcriptional activity. Mechanistically, the low complexity sequence domain of FUS targets the coiled-coil domain of TAZ in a phosphorylation-regulated manner, which ensures the liquidity and dynamicity of TAZ condensates. In cells lacking FUS, TAZ condensates transition into gel-like or solid-like assembles with immobilized TAZ, which leads to reduced expression of target genes and inhibition of pro-tumorigenic activity. Thus, our findings identify a chaperone-like function of FUS in Hippo regulation and demonstrate that appropriate biophysical properties of transcriptional condensates are essential for gene activation.
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Nature Research
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Nature Cell Biology
vol. 26, no 1
vol. 26, no 1
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1465-7392