Circular RNA Aids Heart Attack Recovery

While some RNA molecules carry instructions for making proteins, most are not involved in protein production. Among these noncoding RNAs are the recently discovered circular RNAs, so-named because of their unusual ring shape.

Circular RNAs, like other noncoding RNAs, were previously thought to be nonfunctional, but recent evidence suggests otherwise. Circular RNAs may, in fact, act like sponges to “soak up” (or bind) other molecules, including microRNAs and proteins. In a study published today in Nature Communications, researchers describe a circular RNA that plays a critical role in tissue repair after heart attack, thanks to its ability to “soak up” harmful molecules.

“We discovered that a circular RNA known as circFndc3b, when added therapeutically to the injured heart after surgically induced heart attack in mice, enhances cardiac repair and helps restore heart function,” explains senior author Raj Kishore at LKSOM. “We attributed these effects of circFndc3b to its ability to function like a ‘sponge,’ binding a protein called FUS that mediates cell death and reduces vascular growth, which hinders heart tissue repair.”

The team focused their investigation on circFndc3b after finding that this particular circular RNA was significantly decreased in the hearts of mice that had experienced a heart attack. “This observation led us to wonder whether the change in circFndc3b expression meant that it was important functionally in the heart,” Kishore says.

To investigate this possibility, the researchers injected a gene product to induce circFndc3b overexpression into the heart in mice after heart attack. Subsequent examination showed that within eight weeks of injection, treated mice experienced gains in heart function and in survival compared to their untreated counterparts. There was also evidence within heart tissue that new blood vessels had started to form, greatly aiding the tissue repair process.

The findings offer insight into circular RNAs and the significance of their potential role as molecular sponges that limit the activity of damaging molecules. “CircFndc3b specifically soaked up an RNA binding protein that suppresses blood vessel formation,” Kishore explains. “In doing so, it made way for new vessels to grow.”

The researchers are now in the process of developing a large animal model to further investigate the therapeutic potential of circFndc3b. Additionally, they want to begin analyzing plasma samples from patients just after heart attack to investigate whether specific circulating RNAs could serve as biomarkers for heart disease or injury and to get a better sense of their clinical significance.