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arXiv 1605.03434physics.bio-phq-bio.SC
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分子马达在拥挤轨道上的滑动:核糖体阅读框在RNA模板上的移动

Slip of grip of a molecular motor on a crowded track: Modeling shift of reading frame of ribosome on RNA template

Bhavya Mishra, Gunter M. Schütz, Debashish Chowdhury

摘要:

我们开发了一个随机模型的程序化移码核糖体合成蛋白质,同时沿着mRNA模板移动。正常情况下,核糖体的阅读框以一步一步的方式解码mRNA上连续的核苷酸三联体。我们专注于核糖体阅读框的程序性移位,向前或向后,只有一个核苷酸的融合蛋白的结果;它发生时,核糖体暂时失去了它的抓地力,其mRNA的轨道。特殊的“光滑”核苷酸序列以及mRNA链的下游二级结构被认为在程序性移码中起关键作用。在这里,我们探讨了迄今为止被忽视的参数在调节-1程序移码中的作用。具体来说,我们证明,移码频率也可以强烈调节的核糖体,所有这些都从事在同一mRNA的同时翻译的密度,在和周围的滑序列。蒙特卡罗模拟支持从随机动力学的平均场分析得到的分析预测。

英文摘要:

We develop a stochastic model for the programmed frameshift of ribosomes synthesizing a protein while moving along a mRNA template. Normally the reading frame of a ribosome decodes successive triplets of nucleotides on the mRNA in a step-by-step manner. We focus on the programmed shift of the ribosomal reading frame, forward or backward, by only one nucleotide which results in a fusion protein; it occurs when a ribosome temporarily loses its grip to its mRNA track. Special "slippery" sequences of nucleotides and also downstream secondary structures of the mRNA strand are believed to play key roles in programmed frameshift. Here we explore the role of an hitherto neglected parameter in regulating -1 programmed frameshift. Specifically, we demonstrate that the frameshift frequency can be strongly regulated also by the density of the ribosomes, all of which are engaged in simultaneous translation of the same mRNA, at and around the slippery sequence. Monte Carlo simulations support the analytical predictions obtained from a mean-field analysis of the stochastic dynamics.

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