Condensation and activator/repressor control of a transcription-regulated biomolecular liquid

Sam Wilken; Gabrielle R. Abraham; Omar A. Saleh

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arXiv · 2410.21624

Condensation and activator/repressor control of a transcription-regulated biomolecular liquid

Sam Wilken·Gabrielle R. Abraham·Omar A. Saleh

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Abstract

Cells operate in part by compartmentalizing chemical reactions. For example, recent work has shown that chromatin, the material that contains the cell's genome, can auto-regulate its structure by utilizing reaction products (proteins, RNA) to compartmentalize biomolecules via liquid-liquid phase separation (LLPS). Here, we develop a model biomolecular system that permits quantitative investigation of such dynamics, particularly by coupling a phase-separating system of DNA nanostars to an in vitro transcription reaction. The DNA nanostars' sequence is designed such that they self-assemble into liquid droplets only in the presence of a transcribed single-stranded RNA linker. We find that nanostar droplets form with a substantial delay and non-linear response to the kinetics of RNA synthesis. In addition, we utilize the compartments generated by the phase-separation process to engineer an activator/repressor network, where the transcription reaction activates the formation of droplets, and then droplets suppress the transcription reaction by segregating transcription components inside them. Our work on transcription-driven liquid-liquid phase separation constitutes a robust and programmable platform to explore non-equilibrium reaction-phase transition dynamics and could also provide a foundation to understand the dynamics of transcriptional condensate assembly in cells.

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Sam Wilken, Gabrielle R. Abraham, Omar A. Saleh. 2024-10-29. Condensation and activator/repressor control of a transcription-regulated biomolecular liquid. https://arxiv.org/abs/2410.21624

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