Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; NSF-Simons Center for Mathematical & Statistical Analysis of Biology, Harvard University, Cambridge, MA 02138, USA.
Cell. 2021 Jan 7;184(1):207-225.e24. doi: 10.1016/j.cell.2020.11.030. Epub 2020 Dec 16.
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.
生物过程的调节通常包含启动和终止该过程的机制，而在已被理解的机制中，这些机制通常涉及反馈控制。转录的调节是一个基本的细胞过程，其中涉及启动的机制已经被广泛研究，但涉及终止的机制则知之甚少。RNA 在转录控制中的潜在作用的建模表明，存在一种非平衡的反馈控制机制，其中低水平的 RNA 促进由静电相互作用形成的凝聚物，而相对高水平的 RNA 则促进这些凝聚物的溶解。来自体外和体内实验的证据支持这样一种模型，即在转录起始的早期步骤中产生的 RNA 刺激凝聚物的形成，而在延伸过程中产生的 RNA 的爆发则刺激凝聚物的溶解。我们提出，转录调节包含一种反馈机制，其中转录产生的 RNA 最初刺激但最终终止该过程。
