Sylvester Comprehensive Cancer Center

UM Researchers Identify Important Enzyme

01.21.2005

The Department of Biochemistry at the University of Miami Leonard M. Miller School of Medicine has identified a component of RNA metabolism that plays a key role in helping cells adapt to changes in their environment. The study was led by Murray P. Deutscher, Ph.D., chairman of the Department of Biochemistry and Molecular Biology, and is published in the January 21 issue of the journal Molecular Cell, http://www.molecule.org/.

Dr. Deutscher found an exoribonuclease, RNase R, which plays a key role in degrading some types of messenger RNA. RNA is the intermediary, or “mediator” between DNA and a cell’s proteins. Ribonucleases are enzymes that control the levels of RNA. Different conditions require different proteins, allowing cells to adapt to a variety of situations. “Different cells make different proteins and that’s why, say, a nerve cell is different from a skin cell,” said Deutscher. Cells also respond to environmental changes – for example, a sudden shift in temperature or nutritional status.

For a cell to respond to changes in its environment, it has to remove or degrade existing RNA to accommodate new RNA with new “orders.” The enzyme identified by Dr. Deutscher and his team is critical to degrading one type of RNA, messenger RNA. This mRNA carries the actual “message” from the DNA, the instructions for how to respond to various situations.

RNase R, the enzyme examined in this study, affects about one-third of messenger RNAs. These mRNAs have an unusually complex shape. “There are certain messenger RNAs that have, at one end, some complicated secondary structure,” said Deutscher. “Those are the ones that are specifically affected by the absence of this enzyme, RNase R. The other two-thirds that don’t have this unusual structure can be degraded by other enzymes.”

“There are as many as 15 to 20 ribonucleases in a simple bacterial cell,” said Deutscher, who studies RNA in the E. coli bacterium, which, because of its relative simplicity, is easier to study than animal cells. However, there are enough similarities among cells in these fundamental processes that any lessons learned could be extended to study in humans. “These ribonucleases have many, many functions, and that’s why the cell needs different ones with different specificities.” While two-thirds of messenger RNAs respond to multiple ribonuclease enzymes, so far, RNase R is the only enzyme identified by scientists that can degrade these complex mRNAs. While this doesn’t yield any disease therapies yet, it does open new areas for study of regulation of gene expression.

“This is very important because you have to understand how normal cells work before you can understand what has gone wrong in a disease process,” said Deutscher, who has been a leading researcher in the RNA field for close to 40 years, and who joined UM as chairman of biochemistry in 1995. “We have to understand enough about what goes on normally to know when something goes wrong. It’s like trying to fix a car when you don’t know how an engine works.”

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