Naked Mole Rats Have Unusual and Efficient Ribosomes

Naked mole rats live as much as nine times longer than the members of other similarly-sized rodent species and are essentially immune to cancer, traits that may be side-effects of evolutionary adaptation to life in oxygen-poor underground burrows. Insofar as there is any consensus on the mechanisms driving naked mole rat longevity, it centers around the membrane pacemaker hypothesis: that the composition of important cell membranes in this species, such as those in mitochondria, makes them more resistant to oxidative damage. That in theory cuts down on some of the forms of stochastic damage that lead to degenerative aging.

Here researchers identify another novel feature in the low-level molecular biology of naked mole rats. This most likely indicates the opening of another line of research into the roots of their longevity:

Why Do Naked Mole Rats Live So Long?

In recent years, Gorbunova and her husband Andrei Seluanov have looked closely at the species, which lives in underground colonies in East Africa, hoping to figure out how exactly it manages to survive so long. As revealed in new research her team published today in Proceedings of the National Academy of Sciences, their team thinks they've found at least part of the answer: naked mole rats have strange ribosomes.

Every one of our cells (and, for that matter, every living organism's cells) converts the genetic instructions present in our DNA into proteins - which control a cell's overall operation - through a process called translation. Tiny microscopic structures called ribosomes handle this translation, reading genetic instructions that specify a particular recipe and churning out the protein accordingly.

The ribosomes in almost every multicellular organism on the planet is made up of two large pieces of RNA, a genetic substance similar to DNA. But last year, one of the Rochester lab's students was isolating RNA from cells taken from the naked mole rats when he noticed something unusual. When he separated the RNA pieces, instead of seeing two distinct pieces of ribosomal RNA, he saw three.

After a variety of testing confirmed that it wasn't an experimental error, they decided to look more closely at the potential effects of this unusual structure. It turned out that, compared to mouse ribosomes, these three-part structures made between four and forty times fewer errors during the translation process. At this point, it's unclear how exactly that might lead to longer lifespans, but the researchers believe it plays a key role.

Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage

Molecular mechanisms responsible for differences in longevity between animal species are largely unknown. Here we show that the longest-lived rodent, the naked mole-rat, has more accurate protein translation than the mouse. Furthermore, we show that the naked mole-rat has a unique fragmented ribosomal RNA structure. Such cleaved ribosomal RNA has been reported for only one other species of mammal.

Although we cannot directly test whether the unique 28S rRNA structure contributes to the increased fidelity of translation, we speculate that it may change the folding or dynamics of the large ribosomal subunit, altering the rate of GTP hydrolysis and/or interaction of the large subunit with tRNA during accommodation, thus affecting the fidelity of protein synthesis. In summary, our results show that naked mole-rat cells produce fewer aberrant proteins, supporting the hypothesis that the more stable proteome of the naked mole-rat contributes to its longevity.

The first thing I would do with this new finding, if I had a laboratory and time to burn, is to look at the ribosomes of blind mole rats, a similar species that seems to have evolved its own mechanism for cancer resistance that is conceptually similar to that of the naked mole rat but different in detail. It would be interesting to see if they also have unusual ribosomes, with the most beneficial outcome being that they do not, meaning there may be a good opportunity for comparison studies.

Comments

Naked mole rats are awesome!

Posted by: Nathan Voodoo at September 30th, 2013 5:57 PM

While we're on the subject of naked mole rats, I was reading in this linked article earlier about how NMR cells transfected with SV40 Ras went into crisis and eventually completely died rather than going into tumorigenesis, UNTIL hTERT was also introduced into these cells - they were then able to become full-blown tumors.

I wonder if the NMR's telomerase works differently from our own...

Posted by: Seth at October 4th, 2013 1:53 AM

I think researches demonstrated very well the fact that Naked mole-rat (NMR) 28S rRNA has higher fidelity of translation compared to mouse rRNA. Enhanced translational fidelity contributes to longevity and cancer resistance in naked mole rats. Science structure of 28S rRNA in NMR has no close homologues among other species I was wondering if somebody investigated at the molecular level specific differences that make naked mole –rat rRNA more efficient.

It was mentioned in the post that changing in composition of important membranes (like inner mitochondrion) caused by oxidative damage is associated with aging. If longevity is associated with resistance to oxidative damage in cell membranes are there any evidence that naked mole-rats cell membranes have higher resistance to oxidative damage than cell membranes of similar animals?

Posted by: Anna Grinitsyna at December 3rd, 2013 6:04 PM

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