A rule-based kinetic model of RNA polymerase II C-terminal domain phosphorylation.
A rule-based kinetic model of RNA polymerase II C-terminal domain phosphorylation.
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DOI：
10.1098/rsif.2013.0438
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发表时间：
2013-09-06
期刊：
影响因子：
--
通讯作者：
Beggs JD
中科院分区：
文献类型：
--
作者：
Aitken S;Alexander RD;Beggs JD
许多RNA加工途径的复杂性使得传统的系统建模方法不足以代表所涉及的所有分子种类。我们表明，基于规则的建模允许一个复杂的RNA信号通路的详细模型被定义。RNA聚合酶II（RNAPII）C-末端结构域（CTD;最大亚基的柔性尾状延伸）的磷酸化将前信使RNA加帽、剪接和3′端成熟与转录延伸和终止偶联，并在整合这些过程中发挥核心作用。CTD的许多七肽重复序列的丝氨酸残基的磷酸化状态作为与启动子的距离的函数沿沿着基因编码区改变。从机理的角度来看，磷酸化的变化和它们在基因上发生的位置都是RNAPII在延长中所花费的时间的函数，因为该间隔为激酶和磷酸酶提供了与CTD相互作用的机会。在此基础上，我们综合现有的数据，建立一个动力学模型的行动，已知的激酶和磷酸酶，以解决磷酸化途径及其动力学。
The complexity of many RNA processing pathways is such that a conventional systems modelling approach is inadequate to represent all the molecular species involved. We demonstrate that rule-based modelling permits a detailed model of a complex RNA signalling pathway to be defined. Phosphorylation of the RNA polymerase II (RNAPII) C-terminal domain (CTD; a flexible tail-like extension of the largest subunit) couples pre-messenger RNA capping, splicing and 3′ end maturation to transcriptional elongation and termination, and plays a central role in integrating these processes. The phosphorylation states of the serine residues of many heptapeptide repeats of the CTD alter along the coding region of genes as a function of distance from the promoter. From a mechanistic perspective, both the changes in phosphorylation and the location at which they take place on the genes are a function of the time spent by RNAPII in elongation as this interval provides the opportunity for the kinases and phosphatases to interact with the CTD. On this basis, we synthesize the available data to create a kinetic model of the action of the known kinases and phosphatases to resolve the phosphorylation pathways and their kinetics.
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影响因子：
16
作者：
Mosley, Amber L.;Pattenden, Samantha G.;Carey, Michael;Venkatesh, Swaminathan;Gilmore, Joshua M.;Florens, Laurence;Workman, Jerry L.;Washburn, Michael P.
通讯作者：
Washburn, Michael P.
DOI：
10.1073/pnas.0809908106
发表时间：
2009-04-21
影响因子：
11.1
作者：
Feret, Jerome;Danos, Vincent;Fontana, Walter
通讯作者：
Fontana, Walter
影响因子：
5.6
作者：
Palancade, B;Marshall, NF;Dubois, MF
通讯作者：
Dubois, MF
影响因子：
--
作者：
Maus C;Rybacki S;Uhrmacher AM
通讯作者：
Uhrmacher AM
影响因子：
16
作者：
Buratowski S
通讯作者：
Buratowski S