Versatile Molecule with a New Role in Genome Maintenance

A groundbreaking discovery by Georgia Tech researchers reveals a hidden function of RNA, reshaping our understanding of genetics, health, and evolution. This could pave the way for transformative treatments for cancer and neurological diseases.

The most well-known function of RNA molecules is as messengers for protein synthesis. They transport DNA's genetic instructions to ribosomes, which are the internal factories that convert amino acids into the proteins required for a variety of cellular processes.

However, Storici's group discovered that RNA can also aid cells in repairing double-strand breaks, or DSBs, which are a severe type of DNA damage.

A DSB indicates that the DNA helix's two strands have been broken. Although cells are capable of making repairs, a double-strand break (DSB) is a serious injury that, if left untreated, can result in mutations, cell death, or cancer. (Interestingly, DSBs can result from cancer treatments like radiation and chemotherapy.)

The chemicals and processes behind damaged DNA repairs are the focus of Storici's research as a professor at the School of Biological Sciences. She and her colleagues found that RNA might have been used as a template for DSB repair ten years ago.

Now we have learned that RNA can directly promote DSB repair mechanisms.”

Francesca Storici, School of Biological Sciences, Georgia Institute of Technology

Storici's lab teamed with mathematics experts in Nataša Jonoska's lab at the University of South Florida.

They are all affiliated with Georgia Tech's Southeast Center for Mathematics and Biology. They describe their findings in the journal Nature Communications.

These findings open up a new understanding of RNA's potential role in maintaining genome integrity and driving evolutionary changes.”

Francesca Storici, School of Biological Sciences, Georgia Institute of Technology

The researchers visualized millions of DSB repair events using variation-distance graphs, which provided a thorough overview of sequence variants. The plots showed significant variations in healing patterns based on the site of the DSB. This mathematical method also revealed significant variations in repair effectiveness, suggesting that RNA may be able to influence the results of DSB 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.”

Nataša Jonoska, Department of Mathematics and Statistics, University of South Florida

Molecular Grunt Work

A DSB in DNA is comparable to a load-bearing beam in a structure collapsing. To guarantee the stability of the building or the DNA, a meticulous, accurate repair is required. To stop more damage or mutation, the fragments must be precisely reassembled.

Having a trustworthy foreman on the construction site is essential when repairing a damaged building. Something quite similar is needed for a DSB.

“A key mechanism we identified is that RNA can help position and hold the broken DNA ends in place, facilitating the repair process,” explained Storici, whose team conducted the research in both human and yeast cells.

In particular, scientists discovered that the fragmented DNA segment and RNA molecules can fit together like a puzzle. Beyond its usual coding role, RNA serves as a scaffold or guide when it exhibits this type of complementarity with the DNA break site, directing the cellular machinery where repairs should be made. Cells have developed intricate DSB-fixing processes over millennia, each of which works like a different tool in the same toolbox.

Storici's group demonstrated that RNA can affect the tools employed depending on how well it complements the broken DNA strands. This indicates that RNA serves as both a foreman and a laborer in the process of DNA repair and is also the crucial messenger for protein synthesis.

Better knowledge of RNA's function in DNA repair may lead to new methods for enhancing repair processes in healthy cells, which could lessen the negative effects of radiation and 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,” said Storici.

The findings of Storici's and other researchers' ongoing investigation into the role of RNA in DNA repair may have a long-term effect on evolution and human health. Better gene therapies, novel cancer treatments, and anti-aging techniques are all part of this, as is the capacity to affect how organisms evolve and adapt.