RNA Dynamics Regulate Transcriptional Condensate Vivacity to Drive Gene Coordination

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Transcriptional condensates (TCs) regulate gene expression, particularly super-enhancer (SE)-driven transcription crucial for cell identity.
• The dynamic physical properties of TCs and their role in transcriptional regulation are not fully understood.

Purpose of the Study:

• To investigate the role of enhancer RNA (eRNA) dynamics and RNA exosome activity in maintaining TC integrity and function.
• To elucidate the regulatory axis linking RNA turnover, TC properties, and transcriptional coordination.

Main Methods:

• Depletion of RNA exosome in embryonic stem cells.
• Live-cell imaging and multi-omics analyses.
• Computational modeling.

Main Results:

• RNA exosome depletion disrupts TC integrity, affecting Mediator and Pol II colocalization.
• Perturbed TCs lead to altered transcriptional regulator loading, increased transcriptional noise, and diminished coordinated gene expression.
• RNA turnover dynamically modulates TC fluidity, promoting chromatin contacts and coordinated transcriptional bursts.

Conclusions:

• RNA exosome-mediated eRNA turnover is essential for maintaining TC fluidity and stability.
• Dynamic TC properties are critical for precise transcriptional control, cellular homeostasis, and cell identity.
• RNA-dependent condensate dynamics serve as a quality-control mechanism for global transcriptional coordination.