An essential feature of living organisms is double-stranded DNA, the double-helical molecule that stores our genetic information. Despite the abundance of knowledge we have about the DNA double-helix, we know much less about another double-helix, double-stranded RNA (dsRNA). Dr. Brenda Bass, Distinguished Professor of Biochemistry at the University of Utah School of Medicine, has spent most of her career uncovering the functions of this enigmatic molecule.

Viruses have long been known to produce dsRNA, and when dsRNA binding proteins (dsRBPs) in our bodies bind viral dsRNA they send an SOS that initiates an immune response to fight the infection. For many years it was thought that animals, including humans, did not make their own dsRNA. However, over the past 15 years Dr. Bass and her laboratory have discovered thousands of dsRNAs in many different cells, including those of the human brain and the small worm called Caenorhabditis elegans. The existence of this dsRNA raises two questions: What are the functions of dsRNA in our cells, and how do our cells tell the difference between our dsRNA and that from a virus? Research in Dr. Bass’ laboratory revolves around these two questions.

Dr. Bass is motivated by discovery; she explains that she would “rather tackle a mystery that others have been unable to solve, than make a contribution to an established field.” Therefore, by pursuing the unexpected in the hopes of expanding the boundaries of knowledge and creating new fields, Dr. Bass impacts society by enhancing the rate of scientific progress. Early in her career, as a graduate student, she discovered that certain RNA molecules, or ribozymes, could catalyze reactions using the same principle of catalysis as protein enzymes. This set the stage for a decade of intense study of ribozyme catalysis. As she has continued through her professional career, her seminal observations have lead to the creation of new fields and discoveries, which were recently recognized by her election to the National Academy of Sciences. With a constant interplay between experiments performed in vitro, with test tubes, and those involving in vivo studies in whole animals, Dr. Bass and her diverse team of graduate students and postdoctoral fellows are conducting curiosity-driven research to improve our understanding of the mechanisms underpinning life.

Current research includes:

• Discriminating dsRNA Molecules: In Dr. Bass’ study of two dsRBPs, PKR and Dicer, she and her team have used biochemistry, cell culture studies, and bioinformatics, to determine that features at the ends of dsRNA molecules allow cells to discriminate dsRNA molecules. Intrigued with the idea that the mechanisms that allow such discrimination sometimes goes awry and causes disease, she and her team are investigating the causes and consequences of these mechanistic failures.

• Environmental Cues: A central hypothesis of this project is that dsRNA in our bodies acts to signal environmental changes such as stress, infection and aging. To establish a foundation for these studies, Dr. Bass and her team recently tabulated all of the dsRNA molecules expressed in the tiny worm C. elegans, as well as macrophages of the common house mouse; both of these organisms allow powerful insights that are relevant to human disease. Once in hand these genome-wide databases, or “dsRNAomes” will allow them to monitor how levels of specific dsRNA molecules change in response to various environmental conditions, such as stress.

• Recoding our genetic information: Early in her career Dr. Bass discovered a dsRNA binding protein called an ADAR. ADAR stands for Adenosine Deaminase that acts on RNA, and is an “RNA editing” enzyme--an amazing group of enzymes that can change the sequence of an RNA without changing DNA sequence. ADARs create diversity by allowing one gene to make many different RNA sequences, and ultimately, many different proteins. Dr. Bass continues to study how ADARs carry out their functions, which are particular important in the nervous system.