Translational recoding as a feedback controller: systems approaches reveal polyamine-specific effects on the antizyme ribosomal frameshift.
Translational recoding as a feedback controller: systems approaches reveal polyamine-specific effects on the antizyme ribosomal frameshift.
复制标题
DOI：
10.1093/nar/gkq1349
复制
发表时间：
2011-06
影响因子：
14.9
通讯作者：
Wallace HM
中科院分区：
文献类型：
--
作者：
Rato C;Amirova SR;Bates DG;Stansfield I;Wallace HM
抗酶蛋白Oaz1通过控制多胺生物合成酶鸟氨酸脱羧酶的稳定性来调节多胺（腐胺、亚精胺和精胺）的合成。抗酶mRNA的翻译依赖于多胺刺激的+1核糖体移码，形成一个复杂的负反馈系统，从工程学角度来看，翻译移码事件可被视为细胞内多胺浓度的反馈控制器。在本文中，我们采用综合实验和建模方法，首次对该反馈控制器的特性进行了系统层面的研究。对多胺合成和相互转化受阻的突变酵母菌株进行定量分析，结果显示对不同多胺的移码反应存在显著差异。腐胺和精胺（而非亚精胺）显示出协同刺激移码以及存在多个核糖体结合位点的证据。组合多胺处理表明多胺竞争结合共同的核糖体位点。利用酶动力学和控制工程的概念，建立了翻译控制器的数学模型，以描述核糖体对组合多胺效应的这些复杂反应。一系列模型预测中的每一个都成功地通过在S - 腺苷甲硫氨酸脱羧酶和抗酶突变体以及野生型遗传背景中测量的实验移码频率得到了验证。
The antizyme protein, Oaz1, regulates synthesis of the polyamines putrescine, spermidine and spermine by controlling stability of the polyamine biosynthetic enzyme, ornithine decarboxylase. Antizyme mRNA translation depends upon a polyamine-stimulated +1 ribosomal frameshift, forming a complex negative feedback system in which the translational frameshifting event may be viewed in engineering terms as a feedback controller for intracellular polyamine concentrations. In this article, we present the first systems level study of the characteristics of this feedback controller, using an integrated experimental and modeling approach. Quantitative analysis of mutant yeast strains in which polyamine synthesis and interconversion were blocked revealed marked variations in frameshift responses to the different polyamines. Putrescine and spermine, but not spermidine, showed evidence of co-operative stimulation of frameshifting and the existence of multiple ribosome binding sites. Combinatorial polyamine treatments showed polyamines compete for binding to common ribosome sites. Using concepts from enzyme kinetics and control engineering, a mathematical model of the translational controller was developed to describe these complex ribosomal responses to combinatorial polyamine effects. Each one of a range of model predictions was successfully validated against experimental frameshift frequencies measured in S-adenosylmethionine-decarboxylase and antizyme mutants, as well as in the wild-type genetic background.
登录
查看更多内容
影响因子：
14.9
作者：
Amarantos, I;Kalpaxis, DL
通讯作者：
Kalpaxis, DL
在白色念珠菌返回跨座子TCA2中控制GAG-POL基因表达。
影响因子：
--
作者：
Forbes EM;Nieduszynska SR;Brunton FK;Gibson J;Glover LA;Stansfield I
通讯作者：
Stansfield I
DOI：
10.1073/pnas.91.1.172
发表时间：
1994-01-04
影响因子：
11.1
作者：
BALASUNDARAM, D;DINMAN, JD;TABOR, H
通讯作者：
TABOR, H
DOI：
10.1016/j.bbrc.2005.10.115
发表时间：
2005-12-23
影响因子：
3.1
作者：
Petros, LM;Howard, MT;Atkins, JF
通讯作者：
Atkins, JF
影响因子：
4.1
作者：
Fontaniella, B;Mateos, JL;Legaz, ME
通讯作者：
Legaz, ME