title: MicL, a new σE-dependent sRNA, combats envelope stress by repressing synthesis of Lpp, the major outer membrane lipoprotein.
abstract: In enteric bacteria, the transcription factor σ(E) 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 σ(E)-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 σ(E) activity is sensitive to Lpp abundance and that MicL and Lpp comprise a new σ(E) regulatory loop that opposes membrane stress. Together MicA, RybB, and MicL allow σ(E) to repress the synthesis of all abundant outer membrane proteins in response to stress.
authors.affiliation: Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94158, USA;
authors.forename: Monica S
authors.initials: MS
authors.lastname: Guo
authors.affiliation: Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: Taylor B
authors.initials: TB
authors.lastname: Updegrove
authors.affiliation: Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94158, USA;
authors.forename: Emily B
authors.initials: EB
authors.lastname: Gogol
authors.affiliation: National Center for Biotechnology Information, National Institutes of Health, Bethesda, Maryland 20894, USA.
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Shabalina
authors.affiliation: Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94158, USA;
authors.forename: Carol A
authors.initials: CA
authors.lastname: Gross
authors.affiliation: Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: Gisela
authors.initials: G
authors.lastname: Storz
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis / Q000502:physiology; D058727:RNA, Small Untranslated / Q000235:genetics / Q000378:metabolism*; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics; D012808:Sigma Factor / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; C095020:CutC protein, E coli; D029968:Escherichia coli Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008074:Lipoproteins; C099932:Lpp protein, E coli; C000591290:MicL RNA, E coli; D058727:RNA, Small Untranslated; D038621:Regulatory Sequences, Ribonucleic Acid; D012808:Sigma Factor
keywords: Hfq; copper; cutC; outer membrane homeostasis; sRNA; σE