MicL, a new σ^E-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.