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Multifaceted impact of a nucleoside monophosphate kinase on 5′-end-dependent mRNA degradation in bacteria
Nucleic Acids Research ( IF 16.6 ) Pub Date : 2021-10-07 , DOI: 10.1093/nar/gkab884
Monica P Hui 1, 2 , Joel G Belasco 1, 2
Affiliation  

A key pathway for mRNA degradation in bacterial cells begins with conversion of the initial 5′-terminal triphosphate to a monophosphate, a modification that renders transcripts more vulnerable to attack by ribonucleases whose affinity for monophosphorylated 5′ ends potentiates their catalytic efficacy. In Escherichia coli, the only proteins known to be important for controlling degradation via this pathway are the RNA pyrophosphohydrolase RppH, its heteromeric partner DapF, and the 5′-monophosphate-assisted endonucleases RNase E and RNase G. We have now identified the metabolic enzyme cytidylate kinase as another protein that affects rates of 5′-end-dependent mRNA degradation in E. coli. It does so by utilizing two distinct mechanisms to influence the 5′-terminal phosphorylation state of RNA, each dependent on the catalytic activity of cytidylate kinase and not its mere presence in cells. First, this enzyme acts in conjunction with DapF to stimulate the conversion of 5′ triphosphates to monophosphates by RppH. In addition, it suppresses the direct synthesis of monophosphorylated transcripts that begin with cytidine by reducing the cellular concentration of cytidine monophosphate, thereby disfavoring the 5′-terminal incorporation of this nucleotide by RNA polymerase during transcription initiation. Together, these findings suggest dual signaling pathways by which nucleotide metabolism can impact mRNA degradation in bacteria.

中文翻译:

核苷一磷酸激酶对细菌 5' 端依赖性 mRNA 降解的多方面影响

细菌细胞中 mRNA 降解的一个关键途径始于将最初的 5'-末端三磷酸盐转化为单磷酸盐,这种修饰使转录物更容易受到核糖核酸酶的攻击,核糖核酸酶对单磷酸化 5' 末端的亲和力增强了它们的催化功效。在大肠杆菌中,已知对通过该途径控制降解很重要的唯一蛋白质是 RNA 焦磷酸水解酶 RppH、其异聚伙伴 DapF 和 5'-单磷酸辅助核酸内切酶 RNase E 和 RNase G。我们现在已经确定了代谢酶胞苷酸激酶作为另一种影响大肠杆菌中 5' 端依赖性 mRNA 降解率的蛋白质。它通过利用两种不同的机制来影响 RNA 的 5'-末端磷酸化状态,每一种都依赖于胞苷酸激酶的催化活性,而不仅仅是它在细胞中的存在。首先,这种酶与 DapF 一起作用,通过 RppH 刺激 5' 三磷酸转化为单磷酸。此外,它通过降低胞苷单磷酸的细胞浓度来抑制以胞苷开始的单磷酸化转录物的直接合成,从而不利于在转录起始期间通过 RNA 聚合酶将该核苷酸的 5'-末端掺入。总之,这些发现表明核苷酸代谢可以影响细菌中 mRNA 降解的双重信号通路。它通过降低胞苷单磷酸的细胞浓度来抑制以胞苷开始的单磷酸化转录物的直接合成,从而不利于RNA聚合酶在转录起始期间将该核苷酸的5'末端掺入。总之,这些发现表明核苷酸代谢可以影响细菌中 mRNA 降解的双重信号通路。它通过降低胞苷单磷酸的细胞浓度来抑制以胞苷开始的单磷酸化转录物的直接合成,从而不利于RNA聚合酶在转录起始期间将该核苷酸的5'末端掺入。总之,这些发现表明核苷酸代谢可以影响细菌中 mRNA 降解的双重信号通路。
更新日期:2021-10-07
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