4.8 Article

RNA-Mediated Feedback Control of Transcriptional Condensates

Journal

CELL
Volume 184, Issue 1, Pages 207-+

Publisher

CELL PRESS
DOI: 10.1016/j.cell.2020.11.030

Keywords

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Funding

  1. NIH [GM123511, CA155258, 1F32CA254216-01, GM134734]
  2. NSF [PHY-1743900]
  3. NSF-Simons Center for Mathematical and Statistical Analysis of Biology at Harvard [1764269]
  4. Harvard Quantitative Biology Initiative
  5. Gruss-Lipper postdoctoral fellowship
  6. Rothschild postdoctoral fellowship

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This study discusses the mechanisms of feedback control in regulating biological processes, especially in transcription regulation. Research indicates that RNA in transcription initiation promotes condensate formation, while RNA produced during elongation stimulates condensate dissolution. Therefore, transcriptional regulation involves a feedback mechanism where transcribed RNA both stimulates and arrests the process.
Regulation of biological processes typically incorporates mechanisms that initiate and terminate the process and, where understood, these mechanisms often involve feedback control. Regulation of transcription is a fundamental cellular process where the mechanisms involved in initiation have been studied extensively, but those involved in arresting the process are poorly understood. Modeling of the potential roles of RNA in transcriptional control suggested a non-equilibrium feedback control mechanism where low levels of RNA promote condensates formed by electrostatic interactions whereas relatively high levels promote dissolution of these condensates. Evidence from in vitro and in vivo experiments support a model where RNAs produced during early steps in transcription initiation stimulate condensate formation, whereas the burst of RNAs produced during elongation stimulate condensate dissolution. We propose that transcriptional regulation incorporates a feedback mechanism whereby transcribed RNAs initially stimulate but then ultimately arrest the process.

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