NSF Grant Allows Researcher to Study Element of Fundamental DNA Process

FAYETTEVILLE, Ark. – Daniel Lessner, an assistant professor of biological sciences at the University of Arkansas, was recently awarded a three-year grant for $600,000 from the National Science Foundation to study the role of iron-sulfur clusters in an enzyme essential to life. The award will also support graduate and undergraduate students working with Lessner on the research project.

The enzyme being studied, RNA polymerase, carries out transcription, whereby RNA is produced from DNA, a process that occurs in all organisms.

“This is an enzyme that is essential to life. Every cell has RNA polymerase. Without it, the cell cannot read the information stored in DNA. We’re trying to understand why there are iron-sulfur clusters in certain RNA polymerases,” Lessner said.

A few years ago, scientists determined the structure of an RNA polymerase and discovered that some organisms contain iron-sulfur clusters in the enzyme. The clusters are found in Archaea, one of the oldest forms of microorganisms, as well as higher eukaryotic organisms, such as plants.

“The clusters are not universal, but they are widespread. This level of occurrance suggests that the clusters are doing something important,” Lessner explained.

One hypothesis suggests that the iron-sulfur clusters in RNA polymerase help the cells, and by extension the organism, sense the external environment and modify the synthesis of RNA from the DNA. This method of modifying the expression of the genes may help organisms respond to and survive in sub-standard environments. For example, the iron-sulfur clusters may be used to sense oxygen in methane-producing Archaea called methanogens, which only grow in the absence of oxygen.

“They (the clusters) likely help the organism sense the environment and change the expression of genes in response to effects on metabolism. So we think the clusters help to coordinate the process of transcription in the cell,” Lessner said. “In particular, the microbes that we study are called anaerobes, they grow in the absence of oxygen. When they are exposed to oxygen, their metabolism is inhibited. The iron-sulfur clusters in RNA polymerase may be able to sense the oxygen and change the expression of the genes in response. It may be something along the same lines in higher organisms.”

He hopes to answer the questions of the clusters’ functions by using the methanogen Methanosarcina acetivorans as a model organism to study the role of the clusters in sensing oxygen. By genetically manipulating the methanogen, it will be possible to determine the importance of the clusters for the ability of the methanogen to sense and tolerate oxygen. Because RNA polymerase is universal, results obtained with this methanogen can be extrapolated to understand the role of the clusters in other organisms.