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Proc Natl Acad Sci U S A ; 110(43): 17350-5, 2013 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-24082110

RESUMO

The naked mole-rat (Heterocephalus glaber) is a subterranean eusocial rodent with a markedly long lifespan and resistance to tumorigenesis. Multiple data implicate modulation of protein translation in longevity. Here we report that 28S ribosomal RNA (rRNA) of the naked mole-rat is processed into two smaller fragments of unequal size. The two breakpoints are located in the 28S rRNA divergent region 6 and excise a fragment of 263 nt. The excised fragment is unique to the naked mole-rat rRNA and does not show homology to other genomic regions. Because this hidden break site could alter ribosome structure, we investigated whether translation rate and amino acid incorporation fidelity were altered. We report that naked mole-rat fibroblasts have significantly increased translational fidelity despite having comparable translation rates with mouse fibroblasts. 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.


Assuntos
Fibroblastos/metabolismo , Biossíntese de Proteínas/genética , RNA Ribossômico 28S/genética , RNA Ribossômico 28S/metabolismo , Actinas/metabolismo , Animais , Sequência de Bases , Western Blotting , Células Cultivadas , Eletroforese em Gel de Ágar , Fibroblastos/citologia , Longevidade/genética , Luciferases/genética , Luciferases/metabolismo , Ratos-Toupeira , Dados de Sequência Molecular , Mutação , Taxa de Mutação , Proteoma/genética , Proteoma/metabolismo , Ratos , Proteína S6 Ribossômica/metabolismo , Homologia de Sequência do Ácido Nucleico
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