Horowitz Lab Publishes in PNAS
Proteins are the worker bees of all of the cells that make up our bodies. The proper folding of proteins is essential for the functioning of all cellular processes, and mistakes in the folding process can lead to disease. While nucleic acids (RNA and DNA) have long been known to play a role in protein folding, their direct impact on the process was unclear. A recent academic paper proposes that G-quadruplexes, a type of nucleic acid, can trigger protein folding, illuminating a new strategy for maintaining the health of the proteome.
The paper, G-quadruplexes rescuing protein folding, reports on the results of in vitro protein folding experiments that demonstrate that G-quadruplexes can accelerate protein folding by rescuing intermediates trapped during the process. Time-course folding experiments conducted in Escherichia coli further demonstrate that these G-quadruplexes primarily improve protein folding quality in E. coli, instead of indirectly affecting the process. These findings suggest that short nucleic acids like G-quadruplexes can have a considerable impact on dictating the ultimate folding fate of proteins.
This discovery is significant in the field of healthcare because correctly managing protein folding and aggregation is critical to cellular health. Mistakes in these processes can lead to various diseases, including Alzheimer's and Parkinson's disease. The paper's findings open the possibility of using nucleic acids and ATP-independent chaperones to maintain the health of the proteome, broadening the set of strategies that can be used by the cell to guide protein folding.
Original paper published in Proceedings of the National Academy of Sciences, May 8, 2023 by Son, Huizar Cabral, Huang, Litberg, and Horowitz. Dr. Scott Horowitz is Assistant Professor of Biochemistry and Principal Investigator for the Horowitz Lab at the Knoebel Institute for Healthy Aging at DU.