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Mathematical modeling for transcription of DNA with pausing: Stochastic model with torque, and diffusive transport model.

机译:暂停DNA转录的数学模型:带扭矩的随机模型和扩散运输模型。

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摘要

In fast-transcribing prokaryotic genes, like an rrn gene in Escherichia coli, many RNA polymerases (RNAPs) transcribe the DNA simultaneously. Active elongation of RNAPs is often interrupted by pauses, which has been observed to cause RNAP traffic jams; yet some studies indicate that elongation seems to be faster in the presence of multiple RNAPs than elongation by a single RNAP. We propose that an interaction between RNAPs via the torque produced by RNAP on helically twisted DNA can explain this apparent paradox. We have incorporated the torque mechanism into a stochastic model and simulated transcription both with and without torque. Simulation results illustrate that the torque causes shorter pause durations and fewer collisions between polymerases. Our results suggest that the torsional interaction of RNAPs is an important mechanism in maintaining fast transcription times, and that transcription should be viewed as a cooperative group effort by multiple polymerases. In an effort to further understand transcription, we investigate the Brownian ratchet model for nucleotide translocation. We model elongation as diffusive particle transport in a tilted periodic potential. To incorporate the RNAP pauses, a second periodic potential is added to the first. We present a formula for the mean escape time from a tilted, periodic potential composed of multiple periodic functions as the product of the mean escape time from each individual periodic function. This formula is extended to an arbitrary finite number of periodic functions. Two examples using truncated Fourier series are presented and analyzed.
机译:在快速转录的原核基因中,例如大肠杆菌中的rrn基因,许多RNA聚合酶(RNAP)会同时转录DNA。 RNAP的主动延长通常会被停顿打断,这被认为会导致RNAP交通阻塞。然而,一些研究表明,在存在多个RNAP时,伸长似乎比单个RNAP的伸长快。我们认为,RNAP之间通过RNAP在螺旋扭曲的DNA上产生的扭矩之间的相互作用可以解释这种明显的悖论。我们将扭矩机制纳入了随机模型,并模拟了有无扭矩情况下的转录过程。仿真结果表明,扭矩导致较短的暂停时间和较少的聚合酶之间的碰撞。我们的结果表明,RNAP的扭转相互作用是维持快速转录时间的重要机制,并且转录应被视为多种聚合酶的协同作用。为了进一步理解转录,我们研究了核苷酸易位的布朗棘轮模型。我们在倾斜的周期性势中将伸长建模为扩散粒子传输。为了合并RNAP暂停,将第二个周期性电势添加到第一个。我们提出了由多个周期函数组成的倾斜周期电位的平均逸出时间的公式,作为每个单独周期函数的平均逸出时间的乘积。该公式被扩展为任意有限数量的周期函数。给出并分析了使用截短傅立叶级数的两个例子。

著录项

  • 作者

    Heberling, Tamra Lindsey.;

  • 作者单位

    Montana State University.;

  • 授予单位 Montana State University.;
  • 学科 Applied mathematics.;Molecular biology.;Biophysics.;Mathematics.
  • 学位 Ph.D.
  • 年度 2016
  • 页码 156 p.
  • 总页数 156
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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