RNA is one of the bodies most vital molecules, and it comes in a few forms. For example, messenger RNA fills an essential role in gene expression by copying the sequences of active genes, which are then translated into proteins. Transfer RNA molecules help build proteins by ferrying amino acids to their proper place. Scientists have now revealed yet another critical role for RNA, but this time in the repair of breaks in the genome. The findings have been reported in Nature Communications.
DNA can be damaged in various ways by different things, such as exposure to UV rays, pollution, or chemotherapy. When both strands of the double-stranded DNA molecule are broken, it is known as a double-stranded break (DSB), which is severe. Breaks like this can lead to major problems including certain diseases. But the cell does have ways to detect and repair DSBs.
Professor Francesca Storici of Georgia Tech has been studying mechanisms of DSB repair, and has previously shown that RNA can work as a template for damaged DNA.
“Now we’ve learned that RNA can directly promote DSB repair mechanisms,” said Storici. “These findings open up a new understanding of RNA's potential role in maintaining genome integrity and driving evolutionary changes."
In this work, the investigators used mathematics and variation-distance graphs to analyze millions of DSBs in many different sequences of DNA. This work revealed significant differences in repair mechanisms, which depended on the location of the DSB. There were also changes in the efficiency of repair.
“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,” said study co-author Nataša Jonoska of the University of South Florida.Some of Jonoska's work of is described in the video.
RNA was shown to aid in positioning and holding the ends of broken DNA strands in place, which facilitates repair, explained Storici.
RNA molecules and the broken DNA ends were coming together like puzzle pieces. The RNA then becomes a kind of guide to the cellular machinery that is moving to make the repairs.
The RNA also seems to affect the type of repair mechanism that is employed, depending on how it matches with the DSB ends.
While these findings relate to a basic process in cells, it may inform methods to help cells withstand the effects of chemotherapy.
“RNA has a much broader function than we knew. We still have a lot of research to do into these mechanisms, but this work opens up new ways for exploring how RNA could be harnessed in healthcare, potentially leading to new treatments for cancer and other genetic diseases,” concluded Storici.
Sources: Georgia Institute of Technology, Nature Communications