Healthcare (Commonwealth Union) – A collaborative team of researchers, spearheaded by Francesca Storici from Georgia Tech, has uncovered a novel role for RNA. Their groundbreaking findings have the potential to enhance treatments for conditions such as cancer and neurodegenerative diseases while reshaping our understanding of genetic health and evolution.
Traditionally recognized as messengers in protein synthesis, RNA molecules transport genetic instructions from DNA to ribosomes—the cellular factories that assemble amino acids into proteins essential for various cell functions. However, Storici’s team has revealed that RNA can also play a crucial role in repairing a severe type of DNA damage known as a double-strand break (DSB).
Researchers of the study indicated that a DSB occurs when both strands of the DNA double helix are broken. While cells possess mechanisms to repair some types of damage, DSBs represent significant harm. If left unrepaired or improperly fixed, they can lead to mutations, cell death, or even cancer. Notably, cancer therapies like chemotherapy and radiation often induce DSBs as part of their mechanism of action.
Storici, a professor in the School of Biological Sciences, has spent years investigating the molecular processes involved in repairing damaged DNA. A decade ago, her research revealed that RNA could act as a template to guide the repair of DSBs, opening a new frontier in understanding cellular repair mechanisms.
Storici, whose lab joined hands with mathematics experts from Nataša Jonoska’s team at the University of South Florida. Both groups are part of the Southeast Center for Mathematics and Biology at Georgia Tech, and they detailed their discovery in Nature Communications indicated that RNA can directly promote double-strand break (DSB) repair mechanisms.
Storici further indicated that these findings reveal a new dimension to RNA’s role in preserving genome integrity and shaping evolutionary processes.
The researchers employed variation-distance graphs to map millions of DSB repair events, providing a detailed visualization of sequence variations. These graphs revealed substantial differences in repair patterns based on the position of the DSB.
Additionally, this mathematical method exposed notable disparities in repair efficiency, suggesting RNA may play a crucial role in influencing DSB repair outcomes.
“These findings underscore the critical role of mathematical visualization in understanding complex biological mechanisms and could pave the way for targeted interventions in genome stability and therapeutic research,” added Jonoska.
When a DSB occurs in DNA, it’s comparable to a critical structural support beam in a building collapsing. To maintain the stability and integrity of both the building and the DNA molecule, a meticulous and precise repair process is essential. The damaged segments must be meticulously reassembled to minimize the risk of additional harm or mutations.
In the context of a construction project, having a skilled and trustworthy foreman overseeing the repair work is crucial. Similarly, a DSB in DNA necessitates the presence of an equally reliable and precise repair mechanism. This repair system ensures that the DNA remains functional and undamaged, preventing potential issues that could arise from inaccurate or incomplete repairs.
“A key mechanism we identified is that RNA can help position and hold the broken DNA ends in place, facilitating the repair process,” added Storici, whose team caried out the study in both human as well as yeast cells.
Researchers discovered that RNA molecules can align with damaged DNA segments in a way that resembles puzzle pieces fitting together. When RNA is complementary to a broken DNA site, it serves as a scaffold or guide, going beyond its usual role in coding to direct the cellular machinery toward the repair site. Over time, cells have developed intricate systems to repair double-strand breaks (DSBs), with each mechanism functioning like a specialized tool in a versatile toolkit.
The team led by Storici demonstrated that RNA can influence which repair tools are employed based on its complementarity to the damaged DNA strands. This reveals that RNA is more than just a messenger for protein synthesis—it also acts as both a supervisor and a worker in the DNA repair process.
