Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

Cristina GutierrezCryo-EM studies of the naked mole-rat ribosome

Aging is a multicausal process that is characterized by a decline in genomic integrity, an increased risk for disease, and an increase in mortality. Several insights into mechanisms of aging have been derived using a variety of short-lived model species such as yeast, fruit flies, nematodes, and mice (Kaeberlein & Kennedy, 2010). However, few aging studies focus on long-lived species even though they may elucidate mechanisms involved in resisting aging. Naked mole-rats (Heterocephalus glaber) are the longest living rodents known, with a maximum recorded lifespan of 30 years - they live five times longer than expected based on their body size. And remarkably, they display sustained good health into old age, maintaining their levels of activity, body composition, bone density, metabolic rate, as well as cardiac health, and number of neurons (Edrey et al., 2011). In this regard, the naked mole-rat serves as an interesting model to study healthspan and aging.

Several age-related diseases such as amyotrophic lateral sclerosis, Huntington's disease, and Alzheimer's disease have been implicated in the accumulation of altered proteins and decline in proteome quality. A major factor determining proteome quality is the translational fidelity of the ribosome. Recent studies have shown that the naked mole-rat has a higher fidelity of translation than the mouse, and possesses a unique fragmented 28S ribosomal RNA (Azpurua et al., 2013). Conceivably, this unique structure may contribute to the higher fidelity of translation in the naked mole-rat, as rRNA's interactions with mRNAs and tRNAs play a crucial role in protein synthesis. Here we present, a high-resolution reconstruction (˜4.4 Å) of the naked mole-rat's ribosome. The reconstruction reveals the fragmented 28S rRNA. In addition, three distinct classes representing three conformational states of the ribosome were identified. Taken together, this research will provide a fuller picture of mRNA translation in the naked mole-rat and elucidate the potential effect of the rRNA cleavage on translational fidelity.

    Kaeberlein M, Kennedy B.K. (2010) Hot topics in aging research: protein translation and TOR signaling. Aging Cell 10, 185-190

    Edrey YH, Hanes M, Pinto M, Mele J. Buffenstein R. (2011) Successful aging and sustained good health in the naked mole rat: a long-lived mammalian model for biogerontology and biomedical research. The Institute for Laboratory Animal Research Journal 52, 41-53.

    Azpurua J., Ke Z., Chen I.X., Zhang Q., Ermolenko D.N., Zhang Z.D., Gorbunova V., Seluanov A. (2013) Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage. Proc Natl Acad Sci 110, 17350-17355.

Cristina Gutierrez-Vargas1
Zheng Liu2
Zhonge Ke3
Vera Gorbunova3
Joachim Frank 1, 2, 4

1Department of Biological Sciences
Columbia University
New York, NY 10027
2Department of Biochemistry and Molecular Biophysics
Columbia University
New York, NY 10032
3University of Rochester
Rochester, NY 14627 4Howard Hughes Medical Institute
Columbia University

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