Coenzyme B12 riboswitches are widespread genetic control elements in prokaryotes
Coenzyme B12 riboswitches are widespread genetic control elements in prokaryotes
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DOI：
10.1093/nar/gkh167
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发表时间：
2004-01-01
影响因子：
14.9
通讯作者：
Breaker, RR
中科院分区：
文献类型：
--
作者：
Nahvi, A;Barrick, JE;Breaker, RR
最近的研究已经开始揭示细菌中的许多基本代谢途径是由某些信使 RNA 内的核糖开关调节的。这些核糖开关选择性地结合代谢物并响应配体浓度的变化调节基因表达。此前，我们提供的证据表明，大肠杆菌和鼠伤寒沙门氏菌的 btuB mRNA 均携带辅酶 B-12 依赖性核糖开关，在辅酶浓度升高时，该核糖开关会导致编码的钴胺素转运蛋白的翻译受到抑制。在此，我们使用系统发育分析来定义该核糖开关类的配体结合域的共有序列和二级结构模型。符合该模型的 RNA 结构在革兰氏阳性和革兰氏阴性生物体中广泛存在。此外，我们发现鼠伤寒沙门氏菌的钴胺素生物合成（cob）操纵子的5'-非翻译区（5'-UTR）携带与该共有序列相匹配的RNA基序。该基序的生化和遗传特征证实，RNA 直接结合辅酶 B-12，并且它可能作为遗传控制元件，调节 25 基因操纵子的表达，以在该病原体中产生钴胺素。
Recent studies have begun to reveal that numerous fundamental metabolic pathways in bacteria are regulated by riboswitches residing within certain messenger RNAs. These riboswitches selectively bind metabolites and modulate gene expression in response to changing ligand concentrations. Previously, we provided evidence that the btuB mRNAs of Escherichia coli and Salmonella typhimurium each carry a coenzyme B-12-dependent riboswitch that causes repressed translation of the encoded cobalamin-transport protein at elevated coenzyme concentrations. Herein, we use a phylogenetic analysis to define a consensus sequence and secondary structure model for the ligand- binding domain of this riboswitch class. RNA structures that conform to this model are widespread in both Gram-positive and Gram-negative organisms. In addition, we find that the 5'-untranslated region (5'-UTR) of the cobalamin biosynthesis (cob) operon of S.typhimurium carries an RNA motif that matches this consensus sequence. Biochemical and genetic characterization of this motif confirms that the RNA directly binds coenzyme B-12, and that it likely serves as a genetic control element for regulating expression of the 25-gene operon for cobalamin production in this pathogen.