Functional expansion of a TCA cycle operon mRNA by a 3′ end-derived small RNA
Functional expansion of a TCA cycle operon mRNA by a 3′ end-derived small RNA
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DOI：
10.1093/nar/gky1243
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发表时间：
2018-12
影响因子：
14.9
通讯作者：
M. Miyakoshi;G. Matera;Kanako Maki;Yasuhiro Sone;J. Vogel
中科院分区：
文献类型：
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作者：
M. Miyakoshi;G. Matera;Kanako Maki;Yasuhiro Sone;J. Vogel
摘要细菌中的全球RNA图谱研究已经预测到存在许多小的非编码RNA(SRNAs)，它们从mRNA3‘端被加工出来，通过RNA伴侣Hfq和ProQ来调节其他mRNAs。在这里，我们提出了SDHx(RbbD)的靶点，SDHx是一种依赖于Hfq的sRNA，它是由RNaseE介导的对肠道细菌中TCA循环操纵子sdhCDAB-suABCD的∼10000-NTmRNA的3‘处理而产生的。在电子计算机上的搜索预测，编码醋酸激酶的ackA mRNA是SDHx保守的主要靶点。SDHx通过碱基配对抑制沙门氏菌在醋酸盐上生长过程中AckA的合成。抑制可以通过自然产生的38个核苷酸的SDHx变体来实现，揭示了迄今最短的功能与Hfq相关的sRNA。沙门氏菌SDHx还针对fumB(厌氧延胡索酶)和yfbV的mRNAs，yfbV是一种与ackA相邻的未知功能基因。相反，通过略有不同的种子序列，SDHx可以抑制大肠杆菌中的其他靶标，即katG(过氧化氢酶)和fdoG(需氧甲酸脱氢酶)。本研究阐明了来自中枢代谢的关键操纵子是如何通过3‘附加的sRNA在功能上与其他代谢途径相连的，并支持了mRNA3’UTRs是细菌中调节RNA网络进化的游乐场的观点。
Abstract Global RNA profiling studies in bacteria have predicted the existence of many of small noncoding RNAs (sRNAs) that are processed off mRNA 3′ ends to regulate other mRNAs via the RNA chaperones Hfq and ProQ. Here, we present targets of SdhX (RybD), an Hfq-dependent sRNA that is generated by RNase E mediated 3′ processing of the ∼10 000-nt mRNA of the TCA cycle operon sdhCDAB-sucABCD in enteric bacteria. An in silico search predicted ackA mRNA, which encodes acetate kinase, as a conserved primary target of SdhX. Through base pairing, SdhX represses AckA synthesis during growth of Salmonella on acetate. Repression can be achieved by a naturally occurring 38-nucleotide SdhX variant, revealing the shortest functional Hfq-associated sRNA yet. Salmonella SdhX also targets the mRNAs of fumB (anaerobic fumarase) and yfbV, a gene of unknown function adjacent to ackA. Instead, through a slightly different seed sequence, SdhX can repress other targets in Escherichia coli, namely katG (catalase) and fdoG (aerobic formate dehydrogenase). This study illustrates how a key operon from central metabolism is functionally connected to other metabolic pathways through a 3′ appended sRNA, and supports the notion that mRNA 3′UTRs are a playground for the evolution of regulatory RNA networks in bacteria.