Instituto de Matemática e Estátistica, Universidade de São Paulo, Rua do Matão, 1010, CEP 05508-090, São Paulo - SP, Brazil.
Institute of Complex Systems II, Theoretical Soft Matter and Biophysics, Forschungszentrum Jülich, 52425 Jülich, Germany.
J Theor Biol. 2019 Feb 7;462:370-380. doi: 10.1016/j.jtbi.2018.11.025. Epub 2018 Nov 27.
We show that non-steric molecular interactions between RNA polymerase (RNAP) motors that move simultaneously on the same DNA track determine strongly the kinetics of transcription elongation. With a focus on the role of collisions and cooperation, we introduce a stochastic model that allows for the exact analytical computation of the stationary properties of transcription elongation as a function of RNAP density, their interaction strength, nucleoside triphosphate concentration, and rate of pyrophosphate release. Cooperative pushing, i.e., an enhancement of the average RNAP velocity and elongation rate, arises due to stochastic pushing which cannot be explained by steric hindrance alone. The cooperative effect requires a molecular repulsion in excess of a critical strength and disappears beyond a critical RNAP density, above which jamming due to collisions takes over. For strong repulsion and at the same time strong stochastic blocking, cooperative pushing at low RNAP densities is suppressed, but a reentrance regime at higher densities appears.
我们表明,在同一 DNA 轨道上同时移动的 RNA 聚合酶(RNAP)分子之间的非位阻分子相互作用强烈决定了转录延伸的动力学。我们专注于碰撞和合作的作用,引入了一个随机模型,该模型允许精确地分析计算转录延伸的静态特性作为 RNAP 密度、相互作用强度、核苷三磷酸浓度和焦磷酸释放速率的函数。由于不能仅用位阻来解释的随机推动,协同推动会增强平均 RNAP 速度和延伸率。协同效应需要超过临界强度的分子排斥,并且在超过临界 RNAP 密度时消失,超过该密度后,由于碰撞而导致的堵塞会接管。对于强排斥和同时强随机阻断,在低 RNAP 密度下协同推动受到抑制,但在更高密度下出现再进入状态。