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Israeli-German study shows circular RNA can encode for proteins

March 27, 2017 00:54

Until now, the molecule has been considered “non coding” to make vital proteins for performing regulatory functions in the body, but, in fact, was found to, indeed, be coding.

Cambrian Explosion

Cambrian Explosion, DNA, human body. (photo credit:YOUTUBE SCREENSHOT)

A team of Israeli and German scientists have discovered a protein-encoding function for circular RNA – a kind of molecule that is highly active in brain cells and could play an important role in aging and neurodegenerative diseases.

This discovery reveals an unexplored layer of gene activity in a type of molecule not previously thought to produce proteins. It also reveals the existence of a new universe of proteins not yet characterized.

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The study, published last week in the prestigious journal Molecular Cell, was led by Prof. Sebastian Kadener of the Hebrew University.

Until now, the molecule has been considered “non coding” to make vital proteins for performing regulatory functions in the body, but, in fact, was found to, indeed, be coding.

Unlike all other known RNA, this molecule forms a closed loop, and, therefore, was labeled circular RNAs (circRNAs). Although circRNA molecules are abundant – in particular in the brain where they accumulate as we age – little is known about their function.

In contrast to messenger RNAs (mRNAs), which are generated from genes and have the information to make proteins, circRNAs were previously thought to perform other duties in the cells.

Now, Kadener and colleagues at the Hebrew University, in collaboration with researchers at the Berlin Institute for Medical Systems Biology at the Max Delbrück Center for Molecular Medicine in Berlin, have demonstrated that circRNAs can encode for proteins.

Prof. Gil Ast, from the human molecular department at Tel Aviv University who was not involved in the current study, said: “This is a very important, promising and timely discovery that gives an important hint of the function of these abundant, yet uncharacterized, RNAs. These findings are very important also due to the possible involvement of circRNAs in brain-related diseases.”

To determine whether circRNAs are translated, the researchers used fruit flies and developed or adapted various techniques from molecular biology, computational biochemistry and neurobiology. They showed that specific circRNAs molecules are bound to ribosomes, the machinery that makes proteins, and they were able to find proteins produced from these molecules.

Kadener, of HU’s biological chemistry department, explained: “By identifying the function of circRNAs, this research helps advance our understanding of molecular biology and can be helpful in understanding aging or neurodegenerative diseases.”

Prof. Nikolaus Rajewsky, of BIMSB/Max Delbrück Center for Molecular Medicine, added: “We think that translation of circRNAs is very interesting and that its prevalence and importance must be further investigated.”
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