Structural and kinetic insights into stimulation of RppH-dependent RNA degradation by the metabolic enzyme DapF.
Structural and kinetic insights into stimulation of RppH-dependent RNA degradation by the metabolic enzyme DapF.
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DOI：
10.1093/nar/gky327
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发表时间：
2018-07-27
影响因子：
14.9
通讯作者：
Serganov A
中科院分区：
文献类型：
--
作者：
Gao A;Vasilyev N;Luciano DJ;Levenson-Palmer R;Richards J;Marsiglia WM;Traaseth NJ;Belasco JG;Serganov A
mRNA 5′端的去保护对于真核生物和原核生物中基因表达的控制至关重要，其活性受与辅助因子相互作用调节的酶控制。在大肠杆菌中，5′-末端依赖性mRNA降解始于RNA焦磷酸水解酶RppH产生单磷酸化5′-末端，其可被DapF（一种参与氨基酸和细胞壁生物合成的二氨基庚二酸差向异构酶）刺激。我们已经确定了RppH-DapF复合物的晶体结构，并测量了RNA脱保护的速率。这些研究表明，DapF以两种方式增强RppH活性，这取决于底物的性质。其对二磷酸化RNA（RppH的主要天然底物）反应性的刺激作用需要足够长的底物以达到复合物中的DapF，而三磷酸化RNA的增强反应性似乎涉及DapF诱导的RppH本身的变化，并且同样随底物长度增加。这项研究为理解细胞代谢和mRNA衰变之间的复杂关系提供了基础，并揭示了与真核生物中去帽活性刺激的惊人相似之处。
Vitally important for controlling gene expression in eukaryotes and prokaryotes, the deprotection of mRNA 5′ termini is governed by enzymes whose activity is modulated by interactions with ancillary factors. In Escherichia coli, 5′-end-dependent mRNA degradation begins with the generation of monophosphorylated 5′ termini by the RNA pyrophosphohydrolase RppH, which can be stimulated by DapF, a diaminopimelate epimerase involved in amino acid and cell wall biosynthesis. We have determined crystal structures of RppH–DapF complexes and measured rates of RNA deprotection. These studies show that DapF potentiates RppH activity in two ways, depending on the nature of the substrate. Its stimulatory effect on the reactivity of diphosphorylated RNAs, the predominant natural substrates of RppH, requires a substrate long enough to reach DapF in the complex, while the enhanced reactivity of triphosphorylated RNAs appears to involve DapF-induced changes in RppH itself and likewise increases with substrate length. This study provides a basis for understanding the intricate relationship between cellular metabolism and mRNA decay and reveals striking parallels with the stimulation of decapping activity in eukaryotes.
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影响因子：
11.1
作者：
Hui MP;Foley PL;Belasco JG
通讯作者：
Belasco JG
影响因子：
16
作者：
Luciano DJ;Vasilyev N;Richards J;Serganov A;Belasco JG
通讯作者：
Belasco JG
影响因子：
16
作者：
Celesnik, Helena;Deana, Atilio;Belasco, Joel G.
通讯作者：
Belasco, Joel G.
影响因子：
4.8
作者：
Hor, Lilian;Dobson, Renwick C. J.;Perugini, Matthew A.
通讯作者：
Perugini, Matthew A.
DOI：
10.1073/pnas.88.22.10109
发表时间：
1991-11-01
影响因子：
11.1
作者：
KAPTAIN, S;DOWNEY, WE;KLAUSNER, RD
通讯作者：
KLAUSNER, RD