Down but Not Out: The Role of MicroRNAs in Hibernating Bats

Abstract

MicroRNAs (miRNAs) regulate many physiological processes through post-transcriptional control of gene expression and are a major part of the small noncoding RNAs (snRNA). As hibernators can survive at low body temperatures (Tb) for many months without suffering tissue damage, understanding the mechanisms that enable them to do so are of medical interest. Because the brain integrates peripheral physiology and white adipose tissue (WAT) is the primary energy source during hibernation, we hypothesized that both of these organs play a crucial role in hibernation, and thus, their activity would be relatively increased during hibernation. We carried out the first genomic analysis of small RNAs, specifically miRNAs, in the brain and WAT of a hibernating bat (Myotis ricketti) by comparing deeply torpid with euthermic individual bats using high-throughput sequencing (Solexa) and qPCR validation of expression levels. A total of 196 miRNAs (including 77 novel bat-specific miRNAs) were identified, and of these, 49 miRNAs showed significant differences in expression during hibernation, including 33 in the brain and 25 in WAT (P≤0.01 &│logFC│≥1). Stem-loop qPCR confirmed the miRNA expression patterns identified by Solexa sequencing. Moreover, 31 miRNAs showed tissue- or state-specific expression, and six miRNAs with counts >100 were specifically expressed in the brain. Putative target gene prediction combined with KEGG pathway and GO annotation showed that many essential processes of both organs are significantly correlated with differentially expressed miRNAs during bat hibernation. This is especially evident with down-regulated miRNAs, indicating that many physiological pathways are altered during hibernation. Thus, our novel findings of miRNAs and Interspersed Elements in a hibernating bat suggest that brain and WAT are active with respect to the miRNA expression activity during hibernation.

Waking the sleeping dragon: gene expression profiling reveals adaptive strategies of the hibernating reptile Pogona vitticeps

“…2b). Tissue-specific miRNA expression has been reported during hibernation in thirteen-lined ground squirrels [33][34][35], little brown bats (Myotis lucifugus) [36][37][38], monito del monte (Dromiciops gliroides) [6], and wood frog (Rana sylvatica) [39] (Fig. 5).…”

The hibernating South American marsupial, Dromiciops gliroides, displays torpor-sensitive microRNA expression patterns

“…A growing number of studies by our lab, and others, have demonstrated the essential role of miRNA differential expression in modulating global gene suppression and coordinating the up-regulation of selected genes in response to torpor, estivation, anaerobiosis, and freezing 27 33 34 35 36 37 38 39 40 41 . To our knowledge, the present study is the first to investigate miRNA expression in relation to torpor in a marsupial species.…”

Up-Regulation of Long Non-Coding RNA TUG1 in Hibernating Thirteen-Lined Ground Squirrels

“…Differential expression of ncRNAs in animal models of cold adaptation has garnered significant interest in the field over recent years. Modulation in expression of ncRNAs, in particular miRNAs, at low temperatures has been reported in small mammalian hibernators [22] , [23] , cold-hardy insects [24] , and freeze-tolerant wood frogs [25] . Unlike miRNAs, lncRNAs have not been explored extensively in models of cold adaptation.…”