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<p>The classical view of gene regulation complexes as stable, modular machines needs amending based on emerging insights into their dynamic nature. Whereas recent advances in structural biology have provided high-resolution snapshots of these complex machines, single-molecule and live-cell imaging techniques reveal a more fluid picture: biological function emerges not from static architectures but from transient, dynamic assemblies that continually exchange their components and whose activity is tuned through kinetic control. In this Perspective, we propose dynamic, reversible assembly as a framework for understanding the mechanisms of RNA processing and gene regulation. Drawing on specific case studies from ribosome biogenesis, spliceosomes, small RNAs and transcription factors, we explore how ribonucleoprotein complexes and transcriptional ensembles form and dissolve in time, how protein intrinsically disordered regions collectively enable transcription factors to achieve specificity, and the kinetic principles underlying the fidelity, adaptability and robustness of cellular processes and their related pathologies. In doing so, we show how molecular interactions are governed by rates rather than by equilibrium affinities, providing a foundation for time-integrated structure–function studies.</p>

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Exchange dynamics and kinetic control of gene regulation complexes

  • 期刊论文

  • 发表日期：

    2026年7月30日

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  • Alexander Johnson-Buck,
  • Adrien Chauvier,
  • Abrar A. Abidi,
  • Djem U. Kissiov,
  • Xavier Darzacq,
  • Robert Tjian,
  • Sarah A. Woodson,
  • Nils G. Walter

摘要

The classical view of gene regulation complexes as stable, modular machines needs amending based on emerging insights into their dynamic nature. Whereas recent advances in structural biology have provided high-resolution snapshots of these complex machines, single-molecule and live-cell imaging techniques reveal a more fluid picture: biological function emerges not from static architectures but from transient, dynamic assemblies that continually exchange their components and whose activity is tuned through kinetic control. In this Perspective, we propose dynamic, reversible assembly as a framework for understanding the mechanisms of RNA processing and gene regulation. Drawing on specific case studies from ribosome biogenesis, spliceosomes, small RNAs and transcription factors, we explore how ribonucleoprotein complexes and transcriptional ensembles form and dissolve in time, how protein intrinsically disordered regions collectively enable transcription factors to achieve specificity, and the kinetic principles underlying the fidelity, adaptability and robustness of cellular processes and their related pathologies. In doing so, we show how molecular interactions are governed by rates rather than by equilibrium affinities, providing a foundation for time-integrated structure–function studies.