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).

Additional Metadata
Keywords Antisense RNA, Hibernation, HIF-1α, Hypoxia response, MicroRNA, Non-coding RNA
Persistent URL dx.doi.org/10.1007/s00360-012-0662-y
Journal Journal of Comparative Physiology B
Citation
Maistrovski, Y. (Yulia), Biggar, K.K, & Storey, K. (2012). HIF-1α regulation in mammalian hibernators: Role of non-coding RNA in HIF-1α control during torpor in ground squirrels and bats. Journal of Comparative Physiology B, 182(6), 849–859. doi:10.1007/s00360-012-0662-y