01 October 2013

A long-lived rodent should learn accuracy in protein synthesis

To live a long time, you need to make fewer mistakes

Nadezhda Markina, <url>Our compatriots working at the University of Rochester, Vera Gorbunova and Andrey Seluyanov continue to investigate the phenomenon of longevity of an unusual rodent – a naked digger (Heterocephalus glaber).

He lives for about 30 years, which is phenomenally long for the modest size of his body. Moreover, he still does not get sick and passes away completely healthy, in particular, he never has cancerous tumors.

This phenomenon is extremely attractive to scientists working on the problem of increasing human life expectancy and protection from cancer.

For example, in June of this year Gorbunova and Seluyanov published in Nature their hypothesis that the high-molecular form of hyaluronic acid, which is very abundant in its fibroblasts, protects the naked digger from cancer. A year earlier, other researchers suggested that the secret of the rodent lies in the increased content of a certain protein NRG-1 (neuregulin-1, neuroprotector protein – VM).

Approaching the naked digger from different sides, scientists are puzzling over what would be useful for us to learn from him in order to live a long time and not get sick. Judging by the results of a new study by Gorbunova and Seluyanov, which is published in the latest issue of the journal Proceedings of the National Academy of Sciences (Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage), it is worth learning the most fundamental thing – protein synthesis. It turns out that the digger does it much more perfectly than everyone else. The most important thing is that it has fewer errors. Perhaps this is the secret of his longevity.

(For a popular summary of the results of the work , see in the University of Rochester press release: Better protein creation may be the secret of longevity for the world's longest-living rodent – VM.)Scientists have paid close attention to the ribosomes – "protein production machines" – of the naked digger.

According to them, an accident led to the discovery. Biologists examined an animal tissue sample illuminated with a fluorescent dye under a microscope. And they found three dark lines that indicate the concentration of ribosomal RNA (rRNA) molecules, while all other animals had two such lines. Biologists have decided that this indicates hidden defects in the naked digger's rRNA. And then we decided to see how this "defective" rRNA copes with its responsibilities in the process of protein synthesis.

Ribosomal RNA chains form a framework on which the body of two parts of the ribosome is built – the large and small subunits. Changing the shape of this framework affects the organization of ribosome subunits and their work.

As Gorbunova and Seluyanov discovered, the ribosomal RNA framework of the naked digger is uniquely arranged. The rRNA molecule is divided into two parts, and the intermediate part is simply thrown away. The remaining pieces are located close to each other and work as a single mechanism. And this structural change leads to an amazing result.

When the ribosome collects amino acids like beads, building a chain of protein molecules from them, it sometimes makes mistakes, and another amino acid turns out to be in place of one. Such errors disrupt the structure of the protein and its functioning to varying degrees.

In the cells of a naked digger, due to the unique structure of the ribosomal framework, such errors occur 40 times less often than, for example, in mouse cells. "This turns out to be very important, because proteins built without errors allow the body to work more efficiently," says Seluyanov.

Scientists cannot yet answer the question of how exactly the modified ribosomal RNA increases the accuracy of amino acid assembly. Perhaps it's a matter of faster and more coordinated work of ribosomal subunits.

"As a result, as our results have shown, the cells of the naked digger produce fewer defective proteins," the authors of the article write in PNAS. "This confirms the hypothesis that a more stable proteome (the totality of all proteins) of the naked digger contributes to longevity."

Scientists are going to conduct an experiment: split mouse rRNA in two in the same way and see what happens, whether the process of protein synthesis in mouse cells becomes more perfect.

The authors of the work believe that their discovery is also important for medicine. A lot of human diseases are caused by incorrectly or insufficiently working proteins. Perhaps pharmacological methods can influence the synthesis of protein in humans, making it more perfect. And for many years to improve the work of the human body.

Portal "Eternal youth" http://vechnayamolodost.ru01.10.2013

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