Prof. Martin Sheds New Light on RNA Synthesis Process

As you read this, each of the cells in your body is making fresh copies of the RNA required as a blueprint for making new protein molecules. Complex enzymes - molecular machines - tightly regulate the process of copying DNA to RNA, called "transcription," because mistakes can be deadly. Although transcription is key to our present understanding of biology, the changes that occur during the various stages of transcription have long remained poorly understood. How is it that the enzyme-DNA super-structure remains stable during the stringing together (polymerization) of the thousands of building blocks (nucleotides) in a gene? Past studies have focused on forces between the enzyme and its DNA "train track" or on the direct linkages connecting the product RNA with the DNA track.

Recently however, chemists from UMass Amherst have provided new insights into this stability. In an article published in the prestigious journal "Proceedings of the National Academy of Sciences," Prof. Craig Martin and graduate student Yi Zhou present experiments supporting a model for stability in which the RNA is "topologically locked" (knotted) around the DNA. This in turn presents a new problem: with this efficient knot, how is the RNA released at the end of a gene? Building on the work of Jeff Roberts and colleagues at Cornell University, Martin's and Zhou's results demonstrate that in order for the RNA to release, the enzyme first slides forward to de-thread the knot. Understanding such key steps with unprecedented detail is crucial for developing the new class of gene therapies for treating the many disorders involving transcription and gene regulation. Click here to download the PDF.

(June 2007)