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Elemental Mechanism Driving “Transcriptional Pausing”–Which Controls Gene Expression in All Living Organisms–Revealed by Work at UW-Madison; Study Also Reveals New Understanding of RNA Polymerase
A study published online on January 8, 2019 in eLife, and led by University of Wisconsin–Madison Professor of Biochemistry and Bacteriology Robert Landick, PhD, and his research team, reveals, for the first time, the elemental mechanism behind transcriptional pausing, a phenomenon that underlies the control of gene expression in all living organisms. The work also provides new understanding of the enzyme RNA polymerase, an important drug target for treating conditions such as Clostridium difficile infections and tuberculosis. The findings could ultimately improve our understanding of how certain drugs work against the enzyme and aid in actively targeting it. Gene expression is the process by which DNA is translated into all the proteins and other molecules living organisms need. Although it is a process that all introductory biology students learn about very early, scientists are still a long ways from fully understanding it. The process occurs in two steps. Transcription is the first, where RNA polymerase reads the information on a strand of DNA, which is then copied into a new molecule of messenger RNA (mRNA). In the second stage, the mRNA moves on to be processed (“translated”) into proteins by ribosomes. To help control gene expression levels, “transcriptional pausing” by RNA polymerase can occur between the two stages, providing a kind of “roadblock” where transcription may be terminated or modulated by the cell if need be. “A sequence that causes pausing of RNA polymerases in all organisms, from bacteria to mammals, halts the enzyme in a paused state from which longer-lived pauses can arise,” explains Dr. Landick. “As the fundamental mechanism of this elemental pause is not well defined, we decided to explore this using a variety of biochemical and biophysical approaches.”