A Prophage-Encoded Small RNA Controls Metabolism and Cell Division inEscherichia coli.
Hundreds of small RNAs (sRNAs) have been identified in diverse bacterial species, and while the functions of most remain unknown, some regulate key processes, particularly stress responses. The sRNA DicF was identified over 25 years ago as an inhibitor of cell division but since then has remained uncharacterized. DicF consists of 53 nucleotides and is encoded by a gene carried on a prophage (Qin) in the genomes of manyEscherichia colistrains.We demonstrated that DicF inhibits cell division via direct base pairing withftsZmRNA to repress translation and prevent new synthesis of the bacterial tubulin homolog FtsZ. Systems analysis using computational and experimental methods identified additional mRNA targets of DicF:xylRandpykAmRNAs, encoding the xylose uptake and catabolism regulator and pyruvate kinase, respectively. Genetic analyses showed that DicF directly base pairs with and represses translation of these targets. Phenotypes of cells expressing DicF variants demonstrated that DicF-associated growth inhibition is not solely due to repression offtsZ, indicating that the physiological consequences of DicF-mediated regulation extend beyond effects on cell division caused by reduced FtsZ synthesis.IMPORTANCEsRNAs are ubiquitous and versatile regulators of bacterial gene expression. A number of well-characterized examples inE. coliare highly conserved and present in theE. colicore genome. In contrast, the sRNA DicF (identified over 20 years ago but remaining poorly characterized) is encoded by a gene carried on a defective prophage element in manyE. coligenomes. Here, we characterize DicF in order to better understand how horizontally acquired sRNA regulators impact bacterial gene expression and physiology. Our data confirm the long-hypothesized DicF-mediated regulation offtsZ, encoding the bacterial tubulin homolog required for cell division. We further uncover DicF-mediated posttranscriptional control of metabolic gene expression. Ectopic production of DicF is highly toxic toE. colicells, but the toxicity is not attributable to DicF regulation offtsZ.Further work is needed to reveal the biological roles of and benefits for the host conferred by DicF and other products encoded by defective prophages.
Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA; Department of Microbiology, New York University School of Medicine, New York, New York, USA.
Divya
D
Balasubramanian
Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Preethi T
PT
Ragunathan
Department of Physics, Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA; Department of Biochemistry and Molecular Biology, the University of Chicago, Chicago, Illinois, USA.
Jingyi
J
Fei
Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Carin K
CK
Vanderpool
DicB; FtsZ; Hfq; RNase E; cryptic prophage