Frontiers

Published in Science at 19

November 2007

Boris Zinshteyn, C'09, was a science fair champ in high school, but his many awards didn't prepare him for the remarkable accomplishment he would achieve after just one year at Penn. During his sophomore year, Zinshteyn, a student in the Vagelos Scholars Program in the Molecular Life Sciences, co-authored a paper published in Science, one of the world's most prestigious scientific journals.

"It's very nice to know that your research is important," says Zinshteyn with modesty that belies the significance of the paper's findings on the subject of RNA editing.

Enzymes that edit and change the chemical message of RNA allow one gene to have multiple effects, and help account for why complex organisms can sometimes have fewer genes than simpler ones. The study, which Zinshteyn conducted as part of a research team at Philadelphia's Wistar Institute, is the first to show that a special class of RNA called microRNA can undergo editing that results in significant physiological consequences.

The team tested to see if microRNA editing would affect a gene that codes for PRPS1, an enzyme involved in the production of uric acid. They compared PRPS1 production in a colony of "knockout mice" — mice without microRNA editing capabilities — with production in normal control mice. The knockout mice produced double the normal levels of PRPS1 and showed elevated levels of uric acid, which suggests that microRNA plays an important role in balancing uric acid levels. An excess of uric acid in the body can contribute to problems such as gout and damage to sensory neurons.

"You're trying to do something in the lab, and it's not working, so you have to go back and read all the literature and see what other people have done. Then you realize no one has done it before, so you have to figure out how you can solve the problem on your own." - Boris Zinshteyn

Because the PRPS1 gene was randomly selected out of many possible gene targets of microRNA, the paper's findings imply that microRNA editing could have other physiological effects. Understanding these effects may not only shed light on the causes of various disorders, but could also impact medical research that explores the capabilities of microRNA.

"It's really important for people to know that in the human body there are these proteins that can completely change the targets of microRNAs — especially if research is going to move to trials for humans," Zinshteyn says.

Funded by a Vagelos Molecular Life Sciences Scholarship and a Mark & Melissa Simon Scholarship, Zinshteyn continues to put in long hours at the lab studying new aspects of RNA editing. His commitment is fueled by the challenges of researching on the frontiers of knowledge.

"You're trying to do something in the lab, and it's not working, so you have to go back and read all the literature and see what other people have done," Zinshteyn explains. Then you realize no one has done it before, so you have to figure out how you can solve the problem on your own."