Inside every cell, there is a process that helps you stay healthy. Proteins wrap and unwrap DNA, and even a small mistake in this process can cause cancer.
A new study from the University of Chicago shows a new part of this process that is important for human health.
The study, published on October 2, was led by Professor Chuan He at the University of Chicago and Professor Mingjiang Xu at the University of Texas. They found that RNA helps store and organize DNA in cells, through a gene called TET2. This discovery helps explain why many cancers and other diseases involve TET2 mutations. It also suggests new ways to treat these diseases.
“This is a big breakthrough,” said Professor He. “It not only helps us find new treatments but also adds to our understanding of how DNA is controlled.”
RNA discoveries
Professor He’s lab has made many discoveries about how genes are controlled. In 2011, they found that changes to RNA, not just DNA, can affect which genes are active. Since then, they’ve found more ways RNA is involved in this process.
In this new study, they focused on the gene TET2. Scientists have known that when TET2 or related genes have mutations, many problems occur. These mutations are found in 10-60% of leukemia cases and other cancers, but no one knew why.
For years, researchers thought TET2 worked on DNA, but He’s lab found that TET2 actually affects RNA.
When cells copy their DNA, it needs to be neatly packed into chromatin. RNA plays a key role in this process, controlled by TET2 through a process called methylation. The team showed that TET2 controls how often a type of RNA modification, called m5C, occurs. This attracts a protein called MBD6, which helps pack the DNA.
When you’re a baby, TET2 allows chromatin to stay loose so cells can change into different types. But in adults, TET2 tightens up this process. If TET2 doesn’t work properly, it can lead to cancer, especially in the blood and brain.
The team tested human leukemia cells and found that when they blocked MBD6, the cancer cells died.
A new target for cancer treatment
This discovery gives cancer researchers new drug targets.
“What we hope is to develop a drug that targets only cancer cells by focusing on this pathway,” said He. He is working on creating a startup company to make such a drug.
TET2 mutations don’t just lead to cancer. They are also found in some adults over 70 and increase the risk of heart disease, stroke, diabetes, and inflammation, a condition called CHIP.
“These patients don’t have cancer, but their mutant cells are more inflammatory, which raises their risk of heart, liver, and kidney diseases,” said Caner Saygin, an oncologist at the University of Chicago. “If we can get rid of these mutant cells, we could improve their health.”
A big change in understanding
This discovery also changes how we think about gene control. Scientists already knew that a form of RNA methylation called m6A affects gene expression. But now they’ve found that m5C is involved too, and there may be more similar mechanisms.
“This could be just the beginning,” said He. “We think there’s a lot more to learn about how RNA affects genes and cell behavior.”
This research was originally publish at Nature.
