Our DNA faces constant threats from various sources, including cell division errors and external factors like sunlight and smoking. Fortunately, cells have developed sophisticated repair mechanisms to combat this damage. Recent research has uncovered a surprising role played by long non-coding RNA, particularly NEAT1, in maintaining genome stability. Scientists have found that when highly methylated, NEAT1 helps cells recognize and repair broken DNA strands more efficiently. This discovery could potentially lead to new cancer treatments targeting tumors with high NEAT1 expression.

A team of researchers from Julius-Maximilians-Universität Würzburg in Germany has shed light on a new mechanism in the DNA damage response mediated by RNA transcripts. Dr. Kaspar Burger, junior research group leader at the Department of Biochemistry and Molecular Biology, was responsible for this study. Their study, published in Genes & Development, focused on NEAT1, a long non-coding RNA found in high concentrations in many tumor cells. 

“In our study, we focused on so-called long non-coding RNA transcripts. Previous data suggest that some of these transcripts act as regulators of genome stability,” says Kaspar Burger, explaining the background to the work.

The scientists discovered that DNA double-strand breaks increase both the number of NEAT1 transcripts and their N6-methyladenosine marks. This excessive methylation of NEAT1 leads to changes in its secondary structure, allowing it to accumulate at DNA lesions and drive the recognition of broken DNA.

The research team found that NEAT1 doesn't directly repair DNA damage but enables the controlled release and activation of an RNA-binding DNA repair factor. This process allows cells to recognize and repair DNA damage more efficiently. When NEAT1 levels were experimentally suppressed, it resulted in a delayed DNA damage response and increased amounts of DNA damage. These findings not only broaden our understanding of the DNA damage response but also link it more closely with RNA metabolism.

This discovery could have significant implications for cancer therapy, particularly for tumors with high NEAT1 expression. However, further research is needed to determine if these results, obtained in simple cell systems, can be applied to complex tumor models. As our understanding of the role of RNA modifications in gene regulation grows, it may open up new avenues for targeted cancer treatments and other therapies related to genome stability.

Citations:

University of Würzburg. “Scientists Just Discovered an RNA That Repairs DNA Damage – And It’s a Game-Changer.” SciTechDaily, 2 March 2025, https://scitechdaily.com/scientists-just-discovered-an-rna-that-repairs-dna-damage-and-its-a-game-changer/. Accessed 2 March 2025.