Ribosome recycling, diffusion, and mRNA loop formation in translational regulation
Ribosome recycling, diffusion, and mRNA loop formation in translational regulation
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DOI：
10.1016/s0006-3495(03)74518-4
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发表时间：
2003-08-01
影响因子：
3.4
通讯作者：
Chou, T
中科院分区：
文献类型：
--
作者：
Chou, T
我们探索和量化的物理和生化机制，可能是相关的翻译的调节。在从mRNA的39个终止位点延伸和分离后，部分核糖体机器可以扩散回起始位点，特别是如果它被保持在附近，提高整体翻译速率。的mRNA结合的核糖体的延伸步骤建模使用完全不对称排斥过程的精确和渐近的结果。由于完全不对称排斥过程的核糖体注射速率取决于起始位点处的局部浓度，因此从终止端发出的核糖体源可以反馈到起始位点，从而导致稳态核糖体通量的自洽方程组。另外的mRNA结合因子也可以促进环的形成或环化，使起始位点和终止位点非常接近。使用简单的非相互作用的聚合物模型的起始和终止位点之间的距离的概率分布。我们发现，起始，或初始核糖体吸附结合所需的最大吞吐量，可以显着变化取决于某些值的散装核糖体浓度和扩散常数。如果考虑环促进蛋白和起始/终止位点之间的协同相互作用，则可以以非单调的方式进一步调节通量。可以潜在地测试假设的物理机制的实验进行了讨论。
We explore and quantify the physical and biochemical mechanisms that may be relevant in the regulation of translation. After elongation and detachment from the 39 termination site of mRNA, parts of the ribosome machinery can diffuse back to the initiation site, especially if it is held nearby, enhancing overall translation rates. The elongation steps of the mRNA-bound ribosomes are modeled using exact and asymptotic results of the totally asymmetric exclusion process. Since the ribosome injection rates of the totally asymmetric exclusion process depend on the local concentrations at the initiation site, a source of ribosomes emanating from the termination end can feed back to the initiation site, leading to a self-consistent set of equations for the steady-state ribosome throughput. Additional mRNA binding factors can also promote loop formation, or cyclization, bringing the initiation and termination sites into close proximity. The probability distribution of the distance between the initiation and termination sites is described using simple noninteracting polymer models. We find that the initiation, or initial ribosome adsorption binding required for maximal throughput, can vary dramatically depending on certain values of the bulk ribosome concentration and diffusion constant. If cooperative interactions among the loop-promoting proteins and the initiation/termination sites are considered, the throughput can be further regulated in a nonmonotonic manner. Experiments that can potentially test the hypothesized physical mechanisms are discussed.