MicL, a new σE-dependent sRNA, combats envelope stress by repressing synthesis of Lpp, the major outer membrane lipoprotein

• DOI: 10.1101/gad.243485.114
• Publication Date: 2014-07-16T19:07:39Z
• Authors: Monica S. Guo; Taylor B. Updegrove; Emily B. Gogol; Svetlana A. Shaba...; Carol A. Gross; Gisela Storz
• Keywords: Ribonucleic Acid; 0301 basic medicine; 570; outer membrane homeostasis; Biomedical and clinical sciences; 1.1 Normal biological development and functioning; Physiological; Lipoproteins; sigma(E); 610; Sigma Factor; cutC; Regulatory Sequences, Ribonucleic Acid; Stress; Medical and Health Sciences; Hfq; Promoter Regions; 03 medical and health sciences; Genetic; Underpinning research; Stress, Physiological; Genetics; Escherichia coli; Psychology; Promoter Regions, Genetic; Escherichia coli Proteins; Psychology and Cognitive Sciences; Intracellular Signaling Peptides and Proteins; Biological Sciences; σE; Small Untranslated; Biological sciences; Phenotype; copper; Protein Biosynthesis; RNA; RNA, Small Untranslated; Biochemistry and Cell Biology; Generic health relevance; sRNA; Carrier Proteins; Regulatory Sequences; Biotechnology; Developmental Biology; Research Paper; Bacterial Outer Membrane Proteins

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.