Naked Mole Rat Longevity Explained by Higher Translational Fidelity

Naked mole rat longevity linked to translational fidelity
Understanding more about the “translational fidelity” of protein building in the naked mole rat could herald new pharmaceutical treatments

The naked mole rat may not be much in the way of aesthetics, but scientists believe the tiny creatures could hold the key to developing a better understanding of protein synthesis. During a recent study, the findings of which were published in the journal Proceedings of the National Academy of Sciences (PNAS), researchers discovered improved “translational fidelity” in naked mole rats.

The Naked Mole Rat

Small colony of naked rat molesDue to their longevity and resistance to tumor growth, molecular biologists have flocked to discover the creature’s mysterious characteristics.

The naked mole rat (Heterocephalus glaber) inhabits areas of East Africa, with a number of physical traits that allow it to subsist within harsh, underground environments. These three to four inch creatures are adept at burrowing, and live in intricate clusters of arid desert lands. The tunnel systems that are shaped by these remarkable creatures can extend for up to five kilometers, with individuals of a particular network demonstrating a eusocial way of life; that is, naked mole rats share a division of labor and cooperate with one another.

Recently, a research study has been conducted by a group of biologists, based at the University of Rochester, seeking to establish an explanation for the naked mole rats’ astonishingly long lives, which typically span 30 years, with no diminishing health.

Ribosome Structure Affects Translational Fidelity

The group focused their attention on the mammal’s ability to manufacture proteins. Proteins are an integral part of cellular function, and are produced from the genetic blueprints within the cell’s DNA, located in the nucleus.

In order for a cell to create perfect protein structures, they must have a specific primary sequence of amino acids (the subunits of a protein). This initial sequence determines how the protein then folds to form localized sub-structures and, ultimately, its final 3-dimensional configuration. If the correct sequence is not met, these proteins may not be capable of interacting with other cell structures, thereby impairing its normal function.

Vera Gorbunova, one of the team’s researchers, briefly described their ambitions:

“While this is basic research… we hope our findings encourage further studies on protein synthesis.”

Specifically, the research initiative was designed to investigate the primary sites of protein manufacture, called ribosomes. Gorbunova, working alongside her colleague Seluanov, applied dye to a sample of ribosomal RNA (rRNA), when they made a striking discovery – under ultraviolet light, the samples showed three distinct bands.

Normally, two bands are characteristic of the majority of creatures. This led researchers to posit there to be a “hidden break” in the naked rat mole’s rRNA.

When Gorbunova and Seluanov delved deeper, they established that the rRNA molecule, that forms a part of the ribosome’s structure, was splitting at two places. This then caused a small fragment to become discarded.

As rRNA is an integral constituent of the structure of the cell’s ribosomes, the researchers immediately began investigating something called “translational fidelity.” In essence, the ribosome serves as a molecular scaffold, moving along a messenger RNA (mRNA) template to “read” the cell’s desired protein. As the ribosome sweeps across the template, it aids in the production of the correct protein sequence. If this break affects the structure of these protein making machines, could it influence how they operate?

Diagram showing protein translation in cell
Diagram showing the function of the ribosome (grey). tRNA molecules transport amino acids to the ribosome, and bind to a complementary sequence (a three letter code) on the mRNA strand, allowing the ribosome to catalyse its addition.

When monitoring how this affected ribosomal functions, the researchers found there to be no tangible change in protein production speeds. However, in stark contrast, the boon to “translational fidelity” was enormous. The error rate in naked mole rats (i.e. how often an incorrect amino acid is added to the protein) was 40 times lower than that of mice.

According to the Los Angeles Times, Gorbunova indicates how protein synthesis errors can lead to excess protein “junk,” which is linked to age-related pathology:

“This protein can be recycled, in the young, but as we get older, this recycling process also is not perfect, so we start to accumulate this junk that aggregates, and clogs up the cells.”

In the future, the researchers plan to investigate whether introducing this rRNA split in mouse models will lead to greater translational fidelity. Ultimately, it is thought that the study’s findings could lead to the development of radical pharmaceutical treatments that modify protein synthesis in human beings.

The naked mole rat’s longevity may be explained by higher translational fidelity, but can these findings be used to treat age-related diseases? Only time will tell.

By: James Fenner

PNAS Journal Source

University of Rochester Press Release

Los Angeles Times Link

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