In April 1953 James Watson and Francis Crick wrote in the journal Nature: “This structure has novel features which are of considerable biological interest.” In describing the double helix of DNA, they established what has become an axiom in molecular biology—it matters how things are shaped.

That’s why Arun Malhotra, Ph.D., and his colleagues are excited about their latest find, which was published in Molecular Cell in October 2006. They revealed the shape of RNase II, as it appears in the commonly studied bacteria E. coli.

Ribonucleases are enzymes that break up RNA, ribonucleic acid. RNA is a mediator between DNA and proteins in a cell and also makes up macromolecular machines such as ribosomes that produce proteins in all cells.

“Once we have the structure, we can understand how the enzyme works and how it will work on particular RNAs,” explains Malhotra, an X-ray crystallographer who has been at the Miller School for eight years.

Understanding how ribonucleases, or RNases, work is critical to understanding how RNA functions in a cell. There can be as many as 20 different RNases in a simple bacterial cell, but one family of RNases—RNR—plays a critical role in breaking down messenger RNA. Messenger RNA carries instructions from genomic DNA to make individual proteins. The ability to degrade particular RNAs is vital for cells to quickly turn proteins off as they react to environmental changes like sudden shifts in temperature or nutrition.

The other families of RNases in E. coli have been well studied, with shapes described for four of these enzymes by the Malhotra laboratory, but not RNR. Until now.

Malhotra’s team plans on studying the remaining member of the RNR family, RNase R, next. RNase R is expected to be very similar to RNase II but may be even more important.

“Often these enzymes are almost like mechanical devices that act on things,” says Malhotra. “They have domains that can move and grab other molecules and so on.” Knowing how they work at a molecular level is the key to one day being able to use them to treat disease.