MicL, a new σE-dependent sRNA, combats envelope stress by repressing synthesis of Lpp, the major outer membrane lipoprotein.
MicL, a new σE-dependent sRNA, combats envelope stress by repressing synthesis of Lpp, the major outer membrane lipoprotein.
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DOI：
10.1101/gad.243485.114
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发表时间：
2014-07-15
影响因子：
10.5
通讯作者：
Storz G
中科院分区：
文献类型：
--
作者：
Guo MS;Updegrove TB;Gogol EB;Shabalina SA;Gross CA;Storz G
在肠道细菌中，转录因子σE通过诱导膜修复蛋白的合成以及下调膜孔蛋白合成的两种小调节RNA（sRNA）来维持膜稳态。在这里，Storz及其同事鉴定了第三种σ E依赖性sRNA，MicL，从cutC基因编码序列转录。MicL抑制外膜脂蛋白Lpp，并负责先前与cutC损失相关的铜敏感性表型。这一发现对于理解控制外膜稳态以应对压力的网络至关重要。在肠道细菌中，转录因子σE通过诱导参与膜修复的蛋白质的合成和下调丰富的膜孔蛋白的合成的两个小调节RNA（sRNA）来维持膜稳态。在这里，我们描述了第三个σ E依赖性sRNA的发现，MicL（mRNA干扰Lpp的互补RNA调节子），从位于cutC基因编码序列内的启动子转录。MicL被合成为308个核苷酸（nt）的初级转录物，其被加工成80个核苷酸的形式。这两种形式都具有Hfq结合sRNA的典型特征，但令人惊讶的是，它们仅靶向编码外膜脂蛋白Lpp（细胞中最丰富的蛋白质）的单个mRNA。我们表明，铜敏感性表型先前归因于cutC基因的失活，实际上是来自MicL和LPP水平升高的损失。这一观察结果提出了一种可能性，即目前归因于蛋白质缺陷的其他表型是由于不受重视的调节RNA的缺陷。我们还报道了σE活性对Lpp丰度敏感，并且MicL和Lpp组成了一个新的σE调节环，对抗膜应力。云母、RybB和MicL一起允许σE抑制响应于应激的所有丰富的外膜蛋白的合成。
In enteric bacteria, the transcription factor σE maintains membrane homeostasis by inducing the synthesis of membrane repair proteins as well as two small regulatory RNAs (sRNAs) that down-regulate membrane porin synthesis. Here, Storz and colleagues identify a third σE-dependent sRNA, MicL, transcribed from the cutC gene coding sequence. MicL represses the outer membrane lipoprotein Lpp and is responsible for the copper sensitivity phenotype previously associated with cutC loss. This discovery is critical to understanding the networks that control outer membrane homeostasis in response to stress. In enteric bacteria, the transcription factor σE maintains membrane homeostasis by inducing synthesis of proteins involved in membrane repair and two small regulatory RNAs (sRNAs) that down-regulate synthesis of abundant membrane porins. Here, we describe the discovery of a third σE-dependent sRNA, MicL (mRNA-interfering complementary RNA regulator of Lpp), transcribed from a promoter located within the coding sequence of the cutC gene. MicL is synthesized as a 308-nucleotide (nt) primary transcript that is processed to an 80-nt form. Both forms possess features typical of Hfq-binding sRNAs but surprisingly target only a single mRNA, which encodes the outer membrane lipoprotein Lpp, the most abundant protein of the cell. We show that the copper sensitivity phenotype previously ascribed to inactivation of the cutC gene is actually derived from the loss of MicL and elevated Lpp levels. This observation raises the possibility that other phenotypes currently attributed to protein defects are due to deficiencies in unappreciated regulatory RNAs. We also report that σE activity is sensitive to Lpp abundance and that MicL and Lpp comprise a new σE regulatory loop that opposes membrane stress. Together MicA, RybB, and MicL allow σE to repress the synthesis of all abundant outer membrane proteins in response to stress.
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