Circular RNA Mystery Clearing Up: Are They Linked to Aging?

We knew circular RNA does something important. Now thanks to fruit flies, we're a step closer to knowing what that might be.

Mediterranean fruit fly (BioBee)
An Israeli fruit fly. Courtesy of BioBee

The role played by a mysterious genetic element, evolutionarily conserved circles of RNA, became a step clearer as an international group of scientists discovered that they are – in contrast to expectations – translated into protein.  

Where they get translated into protein, which is everywhere, but chiefly in brain cells, has led to the speculation that they may play a role in neurodegenerative conditions, suggest the scientists in Israel and Germany, led by Prof. Sebastian Kadener from the Hebrew University of Jerusalem, in a paper published today in Molecular Cell.

Circular RNA was discovered some years ago. They turned out to be abundant, particularly in the brain and tellingly, they accumulate with age, says the Hebrew University of Jerusalem.

The molecules of circRNA were not thought to be translated into protein, in contrast to non-circular "messenger RNAs" which do exactly that: they are translated into protein. So circRNAs were thought to do something else.

The fact of their high evolutionary conservation indicates they do something important, whatever it is. So the teams set out to elucidate that using flies.

Ask the fly

We did not know that the circRNAs code for protein, and now that we know that, we do not know what the proteins do. But there are strong clues.

As scientists do, they studied what circRNA is up to, and if it is translated, using that genetics lab staple, the Drosophila fruit fly.  Geneticists love Drosophila because they're hardy little beasts, their genetics are extremely well known, they breed like crazy, their life spans are short, and there are no fruit fly rights organizations picketing their houses.

Helped by techniques from molecular biology, computational biochemistry and neurobiology, the scientists showed that specific circRNAs molecules bind to ribosomes, the protein-making factories in cells. They could also show that the proteins were being made from the circRNA code.

Then they discovered that the proteins produced from these circRNAs are present in synapses, the junctions between nerve cells (or nerve cell to muscle cell).

Moreover, the translation of circRNA is triggered by specific signals, they explain, such as extreme hunger – this elucidated by starving the hapless insects for 12 hours.

Starvation and other signals found to cause of circRNAs to be translated into protein are also involved in aging. The scientists therefore suggest a link between circRNA translation, neurodegenerative diseases and aging. Maybe. It remains to be seen if circRNA translation is also triggered by starving students, for example.

It also remains an open question how important circRNA translation is for normal brain function.