Hypoxia-induced downregulation of RNA m6A protein machinery in the naked mole-rat heart

Ingelson-Filpula, W. Aline; Kadamani, Karen L.; Ojaghi, Mohammad; Pamenter, Matthew E.; Storey, Kenneth B.

doi:10.1016/j.biochi.2024.05.017

Biochimie

2024

DOI: 10.1016/j.biochi.2024.05.017

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Hypoxia-induced downregulation of RNA m6A protein machinery in the naked mole-rat heart

W. Aline Ingelson-Filpula,

Karen L. Kadamani,

Mohammad Ojaghi

et al.

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2024

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Cited by 2 publications

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What can naked mole‐rats teach us about ameliorating hypoxia‐related human diseases?

Kadamani,

Rahnamaie‐Tajadod,

Eaton

et al. 2024

Annals of the New York Academy of Sciences

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Ameliorating the deleterious impact of systemic or tissue‐level hypoxia or ischemia is key to preventing or treating many human diseases and pathologies. Usefully, environmental hypoxia is also a common challenge in many natural habitats; animals that are native to such hypoxic niches often exhibit strategies that enable them to thrive with limited O2 availability. Studying how such species have evolved to tolerate systemic hypoxia offers a promising avenue of discovery for novel strategies to mitigate the deleterious effects of hypoxia in human diseases and pathologies. Of particular interest are naked mole‐rats, which are among the most hypoxia‐tolerant mammals. Naked mole‐rats that tolerate severe hypoxia in a laboratory setting are also protected against clinically relevant mimics of heart attack and stroke. The mechanisms that support this tolerance are currently being elucidated but results to date suggest that metabolic rate suppression, reprogramming of metabolic pathways, and mechanisms that defend against deleterious perturbations of cellular signaling pathways all provide layers of protection. Herein, we synthesize and discuss what is known regarding adaptations to hypoxia in the naked mole‐rat cardiopulmonary system and brain, as these systems comprise both the primary means of delivering O2 to tissues and the most hypoxia‐sensitive organs in mammals.

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What can naked mole‐rats teach us about ameliorating hypoxia‐related human diseases?

Kadamani,

Rahnamaie‐Tajadod,

Eaton

et al. 2024

Annals of the New York Academy of Sciences

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The mRNA N6-Methyladenosine Response to Dehydration in Xenopus laevis

Rehman,

Parent,

Storey

2024

Animals

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The African clawed frog, Xenopus laevis, exhibits remarkable adaptations to survive in its arid habitat, including behavioral and metabolic changes during periods of drought. During extreme dehydration, X. laevis undergoes estivation, a state characterized by increased urea and ammonia levels, depression of the metabolic rate, and tissue hypoxia. To understand the molecular mechanisms underlying these adaptations, we investigated the potential role of N6-methyladenosine (m6A), a widespread mRNA modification, in X. laevis during extreme dehydration. We analyzed the protein levels of key components in the m6A pathway, including writers (METTL3, METTL14, and WTAP), erasers (ALKBH5 and FTO), and readers (SRSF3, YTHDF1, YTHDF2, YTHDF3, and eIF3a), in the liver and kidneys of control frogs and frogs that had lost 35 ± 0.93% of their total body water. The relative protein levels generally decreased or remained unchanged, with the exception of YTHDF3, which depicted a protein level increase in the liver. Notable changes included eIF3a, which was downregulated by 26 ± 8% and 80 ± 8% in the dehydrated liver and kidney tissues, respectively. Additionally, the total m6A increased by 353 ± 30% and 177 ± 17% in dehydrated liver and kidney RNA samples, respectively. This study highlights the importance of epigenetic mechanisms in stress tolerance and provides a foundation for further exploration of the role of epigenetics in dehydration tolerance.

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Hypoxia-induced downregulation of RNA m6A protein machinery in the naked mole-rat heart

Cited by 2 publications

References 48 publications

What can naked mole‐rats teach us about ameliorating hypoxia‐related human diseases?

What can naked mole‐rats teach us about ameliorating hypoxia‐related human diseases?

The mRNA N6-Methyladenosine Response to Dehydration in Xenopus laevis

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