Researchers at the University of Virginia (UVA) in the United States have found an explanation for one of the mysteries of human biology that could have important implications for the fight against breast cancer. The study was published in the scientific journal Science Advances.

The mystery is the so-called “G-value paradox”: humans have no more protein-coding genes than a tiny roundworm, yet our bodies and brains are far more complex.

Dr. Hui Li identified an unexpected player in this process: “chimeric” RNAs, which were previously considered cellular junk. New findings show that these molecules are far from useless: they can generate genetic instructions, expanding our cellular “blueprints” beyond genes, and perform important functions in healthy cells.

In Greek mythology, a chimera is a fire-breathing monster made up of parts of a lion, a goat, and a snake; similarly, chimeric RNA combines genetic material from two or more genes. Scientists initially considered these RNAs mere errors, randomly “stitched” pieces of genetic material, or a consequence of cancer. Over time, it became clear that chimeric RNAs are widespread across all tissues and are a normal part of physiology, but exactly what they do remained unclear.

Li and his team discovered that defective chimeric RNAs play an important role in the development of breast cancer. The researchers created an “atlas” of chimeric RNAs in more than 1,000 cancer cell lines and found that these RNAs frequently malfunctioned in primary breast tumors. The scientists suspect that problems with chimeras may also be linked to other cancers and diseases.

To investigate, Li and his team developed an analytical tool—a “prediction pipeline”—to assess the functions of chimeras, and used it to create an atlas of more than 569,000 chimeric RNAs in 1,019 cancer cell lines. The once-dismissed chimeras turned out to be important in both healthy cells and disease: removing chimeras from healthy cells disrupted the normal cell cycle and caused harmful changes that reduced cell survival. This led Li to conclude that chimeric RNAs play a wide variety of critical roles in the cell’s vital processes.

“The findings demonstrate that chimeric RNAs constitute a previously underappreciated layer of gene expression, expanding the functional genome beyond conventional genetics,” Li and his colleagues write.

Doctors have already been able to develop new cancer treatments by targeting specific cancer-causing chimeras, and the new atlas lays the groundwork for advancing this approach by helping researchers understand what chimeras do and how they can be used to improve care for cancer patients.