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

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)

MicroRNA Regulation in Extreme Environments: Differential Expression of MicroRNAs in the Intertidal Snail Littorina littorea During Extended Periods of Freezing and Anoxia

Several recent studies of vertebrate adaptation to environmental stress have suggested roles for microRNAs (miRNAs) in regulating global suppression of protein synthesis and/or restructuring protein expression patterns. The present study is the first to characterize stress-responsive alterations in the expression of miRNAs during natural freezing or anoxia exposures in an invertebrate species, the intertidal gastropod Littorina littorea. These snails are exposed to anoxia and freezing conditions as their environment constantly fluctuates on both a tidal and seasonal basis. The expression of selected miRNAs that are known to influence the cell cycle, cellular signaling pathways, carbohydrate metabolism and apoptosis was evaluated using RT-PCR. Compared to controls, significant changes in expression were observed for miR-1a-1, miR-34a and miR-29b in hepatopancreas and for miR-1a-1, miR-34a, miR-133a, miR-125b, miR-29b and miR-2a in foot muscle after freezing exposure at -6. °C for 24. h (P<0.05). In addition, in response to anoxia stress for 24. h, significant changes in expression were also observed for miR-1a-1, miR-210 and miR-29b in hepatopancreas and for miR-1a-1, miR-34a, miR-133a, miR-29b and miR-2a in foot muscle (P<0.05). Moreover, protein expression of Dicer, an enzyme responsible for mature microRNA processing, was increased in foot muscle during freezing and anoxia and in hepatopancreas during freezing. Alterations in expression of these miRNAs in L. littorea tissues may contribute to organismal survival under freezing and anoxia