Circular RNA makes fruit flies live longer

Date:
July 7, 2020
Source:
Max-Planck-Gesellschaft
Summary:
The molecule influences the insulin signalling pathway and thus
prolongs life.



FULL STORY ========================================================================== Ribonucleic acid, or RNA, is part of our genetic code and present in
every cell of our body. The best known form of RNA is a single linear
strand, of which the function is well known and characterized. But there
is also another type of RNA, so-called "circular RNA," or circRNA, which
forms a continuous loop that makes it more stable and less vulnerable
to degradation. CircRNAs accumulate in the brain with age. Still, the biological functions of most circRNAs are not known and are a riddle for
the scientific community. Now scientists from the Max Planck Institute
for Biology of Ageing have come one step closer to answer the question
what these mysterious circRNAs do: one of them contributes to the ageing process in fruit flies.


========================================================================== Carina Weigelt and other researchers in the group led by Linda Partridge, Director at the Max Planck Institute for Biology of Ageing, used fruit
flies to investigate the role of the circRNAs in the ageing process. "This
is unique, because it is not very well understood what circRNAs do,
especially not in an ageing perspective. Nobody has looked at circRNAs
in a longevity context before," says Carina Weigelt who conducted the
main part of the study. She continues: "Now we have identified a circRNA
that can extend lifespan of fruit flies when we increase it, and it is regulated by insulin signaling." Specific circRNA influences lifespan
via insulin signalling The insulin pathway regulates ageing, metabolism, reproduction and growth in worms, flies and humans. When this pathway
is blocked by different methods, for instance by using genetically
modified flies that lack insulin, the flies live longer. But it is not
known how exactly this happens. The scientists now believe that part of
the answer could lie with the circRNAs. They found a specific circRNA,
called circSulfateless (circSfl), that behaved differently compared
to other circRNAs. CircSfl was expressed at much higher levels in the long-lived fruit flies that lacked insulin as compared to normal flies.

Furthermore, when flies were genetically manipulated to have higher level
of circSfl, these flies also lived longer. These findings show that not
only is circSfl dependent on insulin -- circSfl itself can also directly influence the lifespan of fruit flies.

In the cells the necessary proteins that the body needs for all sorts
of functions are made from normal linear RNAs, but generally not
from circular RNAs. Again, the 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 classical Sfl protein originating from the linear Sfl RNA. We don't know exactly how the circSfl-derived protein influences ageing, but perhaps it interacts with similar proteins as the regular Sfl protein." What does
this mean for ageing research? Carina Weigelt says: "We want to understand
how ageing works and why the flies lacking insulin are long-lived.

It seems like one of the mechanisms is circSfl. We now want to further investigate the ageing process by looking at other circular RNAs also in
other animals." Because circular RNAs also accumulate in the mammalian
brain, these findings most likely also have important implications
for humans.


========================================================================== Story Source: Materials provided by Max-Planck-Gesellschaft. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Carina Marianne Weigelt, Rohan Sehgal, Luke Stephen Tain, Jun Cheng,
Jacqueline Esser, Andre' Pahl, Christoph Dieterich, Sebastian
Gro"nke, Linda Partridge. An Insulin-Sensitive Circular RNA that
Regulates Lifespan in Drosophila. Molecular Cell, 2020; DOI:
10.1016/ j.molcel.2020.06.011 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200707113253.htm

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