Basic work on E. coli identifies two new keys to regulation of bacterial gene expression

MADISON - The cellular process of transcription, in which the enzyme RNA polymerase constructs chains of RNA from information contained in DNA, depends upon previously underappreciated sections of both the DNA promoter region and RNA polymerase, according to work done with the bacterium E. coli and published today (June 16) in the journal Cell by a team of bacteriologists from the University of Wisconsin-Madison.

This fundamental research about a key step in RNA synthesis has important implications for the study of gene expression in other organisms, and adds to the wealth of knowledge about E. coli contributed by scientists from the UW-Madison.

"The kinds of processes that we study in E. coli happen in a wide variety of bacteria of medical, environmental and agricultural importance," notes Rick Gourse, a professor of bacteriology who published the Cell paper along with a team from his lab. "This knowledge can ultimately be put to use in systems that aren't so amenable to investigation, such as bacteria that cause cholera, produce anthrax toxin or lead to ulcers and stomach cancer."

Scientists use model organisms because they are relatively easy to work with and because there is a vast amount of previous knowledge about them. They can then test whether their findings in model organisms hold true in other species, says Gourse, who studies a strain of E. coli that while harmless, is closely related to disease-causing varieties like E. coli 0157:H7.

"Basic research in E. coli is very important," says Gourse. "Much of what we know about gene expression both in bacteria and in higher life forms comes from work performed originally on this model organism." The strain that Gourse works with is one of the most well-studied species in biology and has important ties to the UW-Madison.

In his most recent study, Gourse investigated the interaction between RNA polymerase and promoters from the E. coli chromosome. RNA polymerase reads the information in DNA and transcribes it into chains of RNA, which are later translated into proteins. Promoter regions are specific sequences within the DNA chain that tell RNA polymerase when and where to begin transcription, and how much product to make from specific genes.

Gourse's group found that there is a specific region within DNA promoters that makes contact with a highly conserved but previously underappreciated segment of the sigma subunit of RNA polymerase. While the contact with sigma is very strong at promoters for most genes, it is particularly weak at promoters that make ribosomal RNA, which means that other factors like nutritional and environmental signals ultimately regulate the expression of those genes.

"In this case, regulation is achieved not because the promoter makes a special contact, but because it can't establish contact at all," says Gourse. "This is an example of how sometimes less is more, and a probably very ancient example of one of the methods that arose through evolution to regulate gene expression."

Ribosomal RNA makes up the bulk of ribosomes, the molecular machines that make proteins and are present in huge numbers in all cells. Since so much of the cell's energy is used to make ribosomes, control of ribosomal RNA transcription is particularly crucial to a cell's well-being.

"This work is basic to the growth of all bacteria," says Gourse. "By understanding transcription and control of ribosome synthesis in E. coli, we can understand more about these processes in bacterial species that we need to control, like those that cause disease or make toxins. E. coli is also the workhorse of the biotechnology industry. Understanding E. coli gene expression in detail allows us to harness these cells for producing products of biotechnological importance, like pharmaceuticals."

Gourse's work was supported by the National Institutes of Health, the United States Department of Agriculture, and by Pfizer Biotechnology. His team included graduate student Shanil Haugen; undergraduate Christopher Ward; and senior scientists Wilma Ross and Tamas Gaal.

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Microbiology at UW-Madison benefits from rich research tradition

The latest research from Rick Gourse's lab is another link in the chain of fundamental breakthroughs on the biology of E. coli that have come from UW-Madison scientists.

The genome sequence of E. coli was first published in 1997 by the lab of UW geneticist Fred Blattner. The sigma subunit that directs RNA polymerase to promoters was discovered almost 40 years ago by Dick Burgess, now a UW-Madison professor of oncology but then a graduate student at Harvard with James Watson, who discovered the structure of DNA.

The study of bacterial gene expression is a particular strength of the UW-Madison, with groups led by not only Gourse and Blattner, but also by professors Bob Landick, Dick Burgess, Tom Record, Tricia Kiley, Karen Wassarman and Aseem Ansari, all specializing in E. coli RNA polymerase.

Leading groups of basic researchers like this one have helped make the UW-Madison Microbiology Doctoral Training Program, with more than 80 faculty and trainers and about 120 graduate students, one of the highest-rated microbiology Ph.D. programs in the nation, trailing only Stanford and Harvard in the latest ratings.

In 2007, the bacteriology department as well as the Food Research Institute and the Medical Microbiology and Immunology Program will move into a newly constructed building at UW-Madison. The state-of-the-art facility is designed to foster collaboration and interaction among scientists working on microbial systems, which will help keep UW-Madison at the forefront of this area for years to come.


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