Discovery Will Change The Way Researchers Look At DNA Transcription, Scientists Say

The UNC scientists have found a previously unknown chemical site on a key enzyme that regulates production of the genetic messenger known as RNA. When the chemical site is occupied, it markedly speeds up the process by which the information contained in DNA, which serves as genetic blueprints, is converted into functions critical for maintaining life.

A report on the discovery appears in the July 27 issue of Cell, a scientific journal. Authors are Dr. Dorothy A. Erie, assistant professor of chemistry; Dr. J. Estelle Foster, a former student of Erie’s now at Eli Lilly and Company, the pharmaceutical manufacturer; and chemistry doctoral student Shannon F. Holmes.

“The information for all the genes in an organism is contained in its DNA, which is like a very long book of instructions,” Erie said. “For this information to be translated into function, sections of the DNA must be copied into an RNA chain. The RNA is then translated into proteins that must carry out countless particular functions such as wound healing , which is at the end of a complicated cascade of events in the body.”

Transcription is the process of making RNA chains from DNA, and RNA polymerase is the enzyme responsible for causing and controlling production of the RNA chain, she said. Erie’s laboratory investigates how the enzyme governing the first step in gene expression works.

“Our recent studies have led to discovery of an additional site on RNA polymerase to which the precursor molecule can bind,” the chemist said. “The precursor molecules can be thought of as links in the growing RNA chain.”

In a series of complicated experiments with the enzyme from the bacterium E. coli, she and her students found that when the precursor molecule does not occupy the newly discovered site, the enzyme copies the DNA slowly. When the molecule occupies the site, production of RNA kicks into overdrive. The process then occurs about 10 times faster than it would otherwise.

“Such rapid synthesis is believed to be essential for proper cellular function,” Erie said. “The discovery of this additional binding site, which we call an allosteric site, will dramatically change the view of how transcription is regulated in cells.”

She and others had thought such a site might exist because transcription of large genes would be too slow otherwise, she said. In a sense, the site can be thought of as a way by which the molecule can ignore or bypass biochemical stoplights on a major highway.

Like many scientists elsewhere, Erie’s laboratory concentrates on bacteria because proteins are similar from one organism to the next, and what they learn in bacteria usually applies to other species.

“Many cancers involve over-expression or improper expression of genes, and some are regulated at the level of transcription,” she said. “If we want to understand how these illnesses occur, then we have to understand the details of RNA polymerase, which people have been studying for 40 years. Knowing now that there are two binding sites on the enzyme instead of one will enable scientists to interpret data they collect much more accurately and create a truer picture of what’s going on.”

The National Institute of General Medical Sciences supported the research.