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HIF-1α regulation in mammalian hibernators: role of non-coding RNA in HIF-1α control during torpor in ground squirrels and bats

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Abstract

A potential role for non-coding RNAs, miR-106b and antisense hypoxia inducible transcription factor-1 (HIF-1α), in HIF-1α regulation during mammalian hibernation was investigated in two species, the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) and the little brown bat (Myotis lucifugus). Both species showed differential regulation of HIF-1α during hibernation. HIF-1α protein levels increased significantly in skeletal muscle of both species when animals entered torpor, as well as in bat liver. HIF-1α mRNA levels correlated with the protein increase in bat skeletal muscle and liver but not in squirrel skeletal muscle. Antisense HIF-1α transcripts were identified in skeletal muscle of both hibernators. The expression of antisense HIF-1α was reduced in skeletal muscle of torpid bats compared with euthermic controls, suggesting that release of inhibition by the antisense RNA contributes to regulating HIF-1α translation in this tissue during torpor. The expression of miR-106b, a microRNA associated with HIF-1α regulation, also decreased during torpor in both skeletal muscle and liver of bats and in ground squirrel skeletal muscle. These data present the first evidence that non-coding RNA provides novel post-transcriptional mechanisms of HIF-1α regulation when hibernators descend into deep cold torpor, and also demonstrate that these mechanisms are conserved in two divergent mammalian orders (Rodentia and Chiroptera).

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Acknowledgments

Thanks go to Dr. J.M. Hallenbeck (NINDS, NIH, Bethesda) and Dr. D. Thomas (Université′de Sherbrooke) for providing ground squirrel and bat tissues, respectively, and to J.M. Storey for editorial review of the manuscript. This work was supported by a Discovery grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada. K.B. Storey holds the Canada Research Chair in Molecular Physiology, K.K. Biggar held an NSERC postgraduate fellowship, and Y. Maistrovski was supported by an NSERC undergraduate summer research award.

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  1. Department of Biology, Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada

    Yulia Maistrovski, Kyle K. Biggar & Kenneth B. Storey

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  1. Yulia Maistrovski
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  2. Kyle K. Biggar
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  3. Kenneth B. Storey
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Correspondence to Kenneth B. Storey.

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Communicated by G. Heldmaier.

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Maistrovski, Y., Biggar, K.K. & Storey, K.B. HIF-1α regulation in mammalian hibernators: role of non-coding RNA in HIF-1α control during torpor in ground squirrels and bats. J Comp Physiol B 182, 849–859 (2012). https://doi.org/10.1007/s00360-012-0662-y

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  • DOI: https://doi.org/10.1007/s00360-012-0662-y

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