Tallahassee, Florida – Scientists at Florida State University have uncovered a critical interaction between a human protein and RNA that could pave the way for new treatments for fibrosis, a disease caused by excessive tissue scarring. The groundbreaking research, conducted at FSU’s Institute of Molecular Biophysics and the Department of Chemistry and Biochemistry, focuses on a protein called LARP6, which is central to the production of type I collagen, a key component of tissues such as skin, bones, and organs.
Fibrosis occurs when the body produces too much collagen, leading to thickened, stiff tissue that can impair organ function. It is involved in a variety of serious health conditions, and until now, there has been no drug available that can slow or halt the progression of the disease. Researchers believe that understanding the interaction between LARP6 and RNA could unlock a new strategy for combating this condition.
The FSU team discovered a previously unknown portion of LARP6 that allows the protein to recognize and bind to RNA with remarkable precision. This interaction has been described by the researchers as being akin to puzzle pieces fitting together, allowing the protein to regulate collagen production in a highly controlled way.
“In the simplest terms, we’re trying to figure out how two molecules, just like LEGO pieces, fit together,” said principal investigator Robert Silvers, an assistant professor in the Department of Chemistry and Biochemistry. “But it’s obviously much more complicated than that, because we’re not just considering the structure of the LEGO pieces and how they fit together, but also how different parts of the LEGO pieces move around, and that all ties directly into functionality.”
LARPs, or La-related proteins, are a superfamily of proteins present in all plants and animals. They bind to RNA, which carries genetic information, helps build proteins, and regulates DNA function. LARP6 is one of five main human LARP proteins, and it specifically plays a key role in collagen biosynthesis. Compared to other LARPs, however, there has been very little research into how LARP6 interacts with RNA at the molecular level.
“Our new ‘LEGO piece’ uses a different kind of interaction with its RNA,” Silvers explained. “It utilizes a different set of rules and the protein uses a different RNA binding site altogether.”
The project began when Silvers and his team were introduced to LARP6 by Branco Stefanovic, a professor at the FSU College of Medicine who has dedicated much of his career to studying fibrosis. The researchers initially attempted several techniques to study the protein, including X-ray crystallography, but ultimately settled on NMR spectroscopy, a method that allows scientists to observe molecules in solution under near-physiological conditions.
“In NMR spectroscopy, we can look at the complex in solution close to its natural environment under physiological conditions,” Silvers said. “NMR spectroscopy is ideal as we can study the dynamics of a molecule as well as its structure.”
NMR spectroscopy uses the magnetic properties of atomic nuclei to reveal detailed information about a molecule’s structure and behavior. This technique was particularly effective for studying LARP6 because the protein is unstable until it binds to RNA, making traditional methods less reliable. Using NMR, the researchers were able to map the precise way LARP6 interacts with RNA and how this interaction directly influences the production of type I collagen.
The implications of this discovery are significant. By targeting the LARP6-RNA complex, scientists may be able to develop drugs that slow or prevent collagen overproduction, offering hope to patients suffering from fibrosis. “Because of its function, the complex between LARP6 and RNA is something that we potentially can develop a drug for, to work against fibrosis,” Silvers said. “There is currently no drug, to my knowledge, that can slow down or stop the progression of fibrosis.”
The study, published in Nucleic Acids Research, represents a significant advance in the understanding of protein-RNA interactions and their role in human disease. It opens a potential pathway for future therapies not only for fibrosis but possibly for other diseases related to collagen overproduction.
This research was funded by the National Institutes of Health, highlighting its importance and potential impact on human health. By revealing the molecular details of LARP6’s interaction with RNA, FSU researchers have provided a roadmap that could lead to innovative treatments for a condition that currently has limited options for patients.
With continued study and drug development, the discovery of this protein-RNA interaction could ultimately change the way fibrosis is treated, offering hope for millions of patients worldwide who live with the debilitating effects of excessive tissue scarring.
