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用化学主方程对突发转录和剪接进行建模。

Modeling bursty transcription and splicing with the chemical master equation.

机构信息

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California.

Division of Biology and Biological Engineering & Department of Computing and Mathematical Sciences, California Institute of Technology, Pasadena, California.

出版信息

Biophys J. 2022 Mar 15;121(6):1056-1069. doi: 10.1016/j.bpj.2022.02.004. Epub 2022 Feb 7.

Abstract

Splicing cascades that alter gene products posttranscriptionally also affect expression dynamics. We study a class of processes and associated distributions that emerge from models of bursty promoters coupled to directed acyclic graphs of splicing. These solutions provide full time-dependent joint distributions for an arbitrary number of species with general noise behaviors and transient phenomena, offering qualitative and quantitative insights about how splicing can regulate expression dynamics. Finally, we derive a set of quantitative constraints on the minimum complexity necessary to reproduce gene coexpression patterns using synchronized burst models. We validate these findings by analyzing long-read sequencing data, where we find evidence of expression patterns largely consistent with these constraints.

摘要

剪接级联反应会在后转录水平改变基因产物,也会影响表达动力学。我们研究了一类从突发启动子模型与有向无环图剪接的耦合模型中涌现出的过程和相关分布。这些解决方案为具有一般噪声行为和瞬态现象的任意数量的物种提供了完整的时变联合分布,为剪接如何调节表达动力学提供了定性和定量的见解。最后,我们使用同步突发模型推导出了一组关于再现基因共表达模式所需的最小复杂度的定量约束。我们通过分析长读测序数据来验证这些发现,在这些数据中,我们找到了与这些约束条件大体一致的表达模式的证据。

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