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Circular RNA helps extend the life of fruit flies

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Circular RNA keeps fruit flies alive longer

The fruit fly Drosophila melanogaster seen under a microscope. Credits: F. Vinken

Ribonucleic acid, or RNA, is part of our genetic code and is found in every cell in our body. The best known form of RNA is a single linear strand whose function is well known and characterized. But there is also another type of RNA, called “circular RNA”, or circRNA, which forms a continuous loop which makes it more stable and less vulnerable to degradation. CRNAs circulate in the brain with age. However, the biological functions of most cRNAs are not known and constitute an enigma for the scientific community. Now scientists at the Max Planck Institute for Biology of Aging have gone a step further to answer the question of what these mysterious cRNAs do: one of them contributes to the aging process of fruit flies.

Carina Weigelt and other researchers from the group led by Linda Partridge, director of the Max Planck Institute for Biology of Aging, used fruit flies to study the role of circular cRNAs in the aging process. “It’s unique, because we don’t really understand what cRNAs do, especially not from an aging perspective. No one has ever looked at cRNAs in a longevity setting before, ”says Carina Weigelt, who conducted the main part of the study. She continues: “Now we have identified a cRNA that can extend the lifespan of fruit flies when we increase it, and it is regulated by insulin signage. “

A specific cRNA influences lifespan via insulin signaling

The insulin pathway regulates aging, metabolism, reproduction and growth of worms, flies and humans. When this path is blocked by different methods, for example by using genetically modified flies that lack insulin, flies live longer. But it is not known exactly how it happens. Scientists now believe that part of the answer may lie in circular cRNAs. They found a specific cRNA, called circSulfateless (circSfl), that behaved differently from other cRNAs. CircSfl has been expressed at much higher levels in long-lived fruit flies that lacked insulin compared to normal flies. In addition, when the flies were genetically engineered to have a higher level of circSfl, these flies also lived longer. These results show that not only does circSfl depend on insulin, but circSfl itself can also directly influence the lifespan of fruit flies.

In cells, the necessary proteins that the body needs for all kinds of functions are made from normal linear RNA, but usually not from circular RNA. Again, scientists found another difference between circSfl and other circular RNAs: a protein is indeed made from circSfl. The exact function of this protein is not known, but Carina Weigelt says: “The circSfl protein is similar but not identical to the classic Sfl protein from linear Sfl RNA. We are not exactly sure how the protein derived from circSfl influences aging, but perhaps interacts with proteins similar to the regular Sfl protein. “

What does this mean for research on aging? Carina Weigelt says, “We want to understand how aging works and why insulin-free flies have a long lifespan. One of the mechanisms seems to be circSfl. We now want to deepen the aging process by examining other circular RNAs also in other animals. “Because circular RNAs also accumulate in the brains of mammals, these results most likely also have important implications for humans.


The structure and degradation of circular RNAs regulate the activation of PKR in innate immunity


More information:
Carina Marianne Weigelt et al. An insulin-sensitive circular RNA that regulates the lifespan of Drosophila, Molecular cell (2020). DOI: 10.1016 / d.molcel.2020.06.011

Provided by
Max Planck Company


Quote: Circular RNA appears to extend the lifespan of fruit flies (2020, June 29) recovered on June 29, 2020 on https://phys.org/news/2020-06-circular-rna-fruit-flies -longer.html

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