A team of researchers at Florida State University has identified a new way in which a human protein interacts with RNA, a finding that could help develop treatments for fibrosis, or tissue scarring.
The study focused on the protein LARP6, which is involved in the production of type I collagen—a substance essential to skin and bone structure. Overproduction of collagen is linked to diseases such as fibrosis. The research revealed a previously unknown part of LARP6 that enables it to recognize and bind to RNA with high specificity.
“In the simplest terms, we’re trying to figure out how two molecules, just like LEGO pieces, fit together,” said Robert Silvers, assistant professor in the Department of Chemistry and Biochemistry and principal investigator on the project. “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 (La-related proteins) are found throughout plants and animals. They attach to RNA—the molecule responsible for carrying genetic information and regulating DNA function—and play roles in various biological processes. Among these proteins, LARP6 regulates collagen biosynthesis but has been less studied compared to other members of its family.
“Our new ‘LEGO piece’ uses a different kind of interaction with its RNA,” Silvers said. “It utilizes a different set of rules and the protein uses a different RNA binding site altogether.”
The team began studying this protein after being introduced to it by Branco Stefanovic from FSU’s College of Medicine. After several attempts using techniques such as X-ray crystallography failed to yield results due to instability issues with LARP6 alone, they turned to NMR spectroscopy.
“In NMR spectroscopy, we can look at the complex in solution close to its natural environment under physiological conditions,” Silvers explained. “NMR spectroscopy is ideal as we can study the dynamics of a molecule as well as its structure.”
NMR spectroscopy leverages magnetic properties within certain nuclei to analyze molecular structures in detail—an approach that proved useful since LARP6 stabilizes only when bound with RNA.
Through this method, researchers determined that LARP6’s interaction with RNA plays an active role in producing type I collagen implicated in fibrosis development. This insight may pave the way for drug development targeting this specific interaction.
“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 research received funding from the National Institutes of Health.
FSU Health is an initiative designed by Florida State University aimed at improving health outcomes across Florida by fostering collaborations between university researchers and clinical partners.
