Exploring New Directions with Ilka Heinemann, PhD
Any microbiology textbook will tell you that DNA replication and RNA transcription always proceed in the same direction and no polymerase (the enzyme responsible for the process) has ever been able to do it in the other direction.
Until now.
Using X-ray diffraction, Ilka Heinemann, PhD, and her team at the Schulich School of Medicine & Dentistry were able to map the tiniest structures of a protein called tRNA(His) guanylyltransferase with its RNA substrate.
Through this, they were able to show is that the protein, responsible for tRNA editing, has a unique property that no one could have predicted. While it has the same structural core as a forward polymerase, it actually works in reverse. The results were published in the December edition of Proceedings of the National Academy of Sciences of the United States of America.
“The implication of this is that it proves that we were wrong in assuming that polymerases can only go in one direction,” she said. “The question now is, if we know it is possible to go in reverse, why doesn’t nature do it the other way?”
When she set out to map the structure of this protein during her postdoctoral fellowship at Yale, she didn’t have any idea that this would be the result.
“That’s what I like about science,” Heinemann said. “When you make really cool discoveries, it isn’t always a result of exactly what you set out to do.”
Heinemann is one of Schulich Medicine & Dentistry’s newest researchers, having joined the Department of Biochemistry as an assistant professor in September.
This discovery has opened up a whole host of new questions for Heinemann and her team. Based on what they have learned from this project, they are now starting to investigate what mechanistically causes this particular polymerase to go in the opposite direction. If they can determine those mechanisms, the next question is whether they can tweak a forward polymerase to go in reverse.
“What I love about the academic setting is that you are free to chase big ideas,” she said. “I think that’s a lot of fun.”
