François Jacob, André Lwoff, and Jacques Monod shared the Noble Prize in Physiology in 1965 for their work elucidating methods that E. coli uses to control the process of turning genes into RNA, but the subject has continued to surprise us since. New work has explored mutations found in the gene encoding part of the bacteria’s RNA polymerase, the enzyme that transcribes DNA into RNA so that the RNA can then be translated into protein. You might expect mutations in something so fundamental to be lethal, but these mutations help the bacteria adapt to media with minimal nutrients.
The mutants were first discovered when researchers forced E. coli to grow on food that lacks complex nutrients. They grew 60 percent faster than regular E. coli in minimal media, but it came at a cost: they grew 17-34 percent slower in richer media. The mutations allowed for a higher metabolic rate and a more efficient use of carbon sources like glycerol. How can damaging a gene responsible for making RNA have such dramatic effects?
The researchers focused on mutations that caused deletions in the "jaw" domain of the RNA polymerase. Such mutations destabilize the open complexes required for starting transcription at a subset of genes, including ribosomal RNA genes, which are essential for making proteins. If the bacteria are not transcribing rRNA, they cannot make new proteins—which is an appropriate response to media that lacks amino acids.
The observed decrease in open complex stability should cause a redistribution of RNA polymerase across the genome from those genes requiring it—like ribosomal RNA genes—to those that do not. This is in fact what the researchers observed: RNA polymerase was not found at rRNA genes. But how did the mutants grow 60 percent faster than wild type bugs with less rRNA?
The decreased binding of RNA polymerase to rRNA promoters is compensated for by an increased elongation rate of the mutants. The mutant polymerases paused less as they moved along the genes' DNA. The combination of the two effects yielded a steady level of rRNA.
The odd thing about this finding is that bacteria often respond to nutrient restriction by upregulating a gene that causes an increase in polymerase pausing. So, it appears there are two distinct mechanisms for responding to stress
Gene expression analysis of the mutant strains revealed an upregulation of genes involved in the transport of zinc ions and a downregulation of genes involved in motility, chemotaxis, cell adhesion, and acid resistance. The adaptive mutations described here effectively reprogram RNA polymerase, giving it altered kinetic properties. It will thus preferentially transcribe a certain set of genes at the expense of others. Identifying which genes get turned on and off will help in further untangling the transcriptional network in these bacteria that has been so illustrative in defining universal methods of transcriptional regulation.