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Synthetic Condensates and Cell-Like Architectures from Amphiphilic DNA Nanostructures
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Investigating the functional components of YAP condensates.

Janelle S Bellot1,2, Siyuan Hao1,2, Yihuan Li1,2

  • 1Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205.

Molecular Biology of the Cell
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Yes-associated protein (YAP) condensates are crucial for cell survival during hyperosmotic stress. New research identifies JUNB and TCF12 as key proteins essential for YAP condensate formation and function.

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Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Yes-associated protein (YAP) condensates play a vital role in cellular responses to hyperosmotic stress.
  • The precise mechanisms by which YAP condensates function remain largely unknown.

Purpose of the Study:

  • To identify proteins that interact with YAP in both diffuse and condensate states.
  • To elucidate the functional roles of YAP-interacting proteins in hyperosmotic stress response.

Main Methods:

  • Proximity-based proteomics was utilized to identify YAP-interacting proteins.
  • Immunofluorescence microscopy was employed to visualize protein localization within YAP condensates.
  • Depletion studies were conducted to assess the necessity of identified proteins for condensate formation and function.

Main Results:

  • YAP condensate formation significantly altered the composition of interacting proteins.
  • YAP condensates transitioned from chromatin clustering to transcriptional activation.
  • JUNB, TCF12, and IFI16 were identified as enriched components of YAP condensates.
  • Depletion of JUNB and TCF12 inhibited YAP condensate assembly and downstream gene expression.

Conclusions:

  • Novel protein components, including JUNB and TCF12, are essential for YAP condensate formation and function.
  • These findings reveal the dynamic roles of YAP condensates in the hyperosmotic stress response.
  • The study provides a basis for developing therapeutic strategies targeting YAP condensates.