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

Yuan L, Geiser F, Lin B, Sun H, Chen J, Zhang S - PLoS ONE (2015)

Bottom Line: 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).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.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.

View Article: PubMed Central - PubMed

Affiliation: Guangdong Entomological Institute, Guangzhou, China; Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangzhou, China; Guangdong Key Laboratory of Integrated Pest Management in Agriculture, Guangzhou, China.

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.

No MeSH data available.


Related in: MedlinePlus

Co-regulation of miRNAs and target mRNAs in the adipocytokine signaling pathway.(A) Expression pattern and relationship of differentially expressed miRNAs (left) and mRNAs involved in the adipocytokine signaling pathway (right, identified by DGE, unpublished data). The expression profile of a miRNA or gene in the brain (HB/AB) and adipose tissue (HA/AA) was calculated by sequence counts (TPM). The red and green colors represent high and low gene expression after comparing the hibernating state vs. the active state. Differentially expressed miRNAs and mRNAs (P≤0.01) during hibernation are linked with red lines; (B) Network of adipocytokine signaling pathway. Red box, predicted target genes of differentially expressed miRNAs that were also identified by DGE; Blue box, predicted target genes of differentially expressed miRNAs, but that were not identified by DGE; Green box, genes identified by DGE.
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pone.0135064.g004: Co-regulation of miRNAs and target mRNAs in the adipocytokine signaling pathway.(A) Expression pattern and relationship of differentially expressed miRNAs (left) and mRNAs involved in the adipocytokine signaling pathway (right, identified by DGE, unpublished data). The expression profile of a miRNA or gene in the brain (HB/AB) and adipose tissue (HA/AA) was calculated by sequence counts (TPM). The red and green colors represent high and low gene expression after comparing the hibernating state vs. the active state. Differentially expressed miRNAs and mRNAs (P≤0.01) during hibernation are linked with red lines; (B) Network of adipocytokine signaling pathway. Red box, predicted target genes of differentially expressed miRNAs that were also identified by DGE; Blue box, predicted target genes of differentially expressed miRNAs, but that were not identified by DGE; Green box, genes identified by DGE.

Mentions: We further examined the adipocytokine signaling pathway to determine the relationship between miRNAs and target mRNAs during hibernation, as adipocytokine signaling is co-regulated by both brain and adipose tissues. Moreover, we searched for mRNAs from our on-going project of digital gene expression (DGE) sequencing to enrich for target genes. DGE sequencing has been conducted on the same animals used here (unpublished data). A total of 64 mRNAs involved in adipocytokine signaling pathway were identified by DGE sequencing (S10 Table, DGE unpublished data). By combining the miRNA and target mRNA expression patterns, we found that 41 of 49 differentially expressed miRNAs regulated the expression of 51 genes, and more than half of the genes in each tissue were up-regulated during hibernation. Among these, the differential expression of three mRNAs (Insulin Receptor Substrate, IRS; Adenosine 5‘-monophosphate (AMP)-activated protein kinase, AMPK; Retinoid X receptor, RXR) was significant (P≤0.01), including IRS over-expression. The others were down-regulated during HA/AA (Fig 4 and S10 Table).


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

Yuan L, Geiser F, Lin B, Sun H, Chen J, Zhang S - PLoS ONE (2015)

Co-regulation of miRNAs and target mRNAs in the adipocytokine signaling pathway.(A) Expression pattern and relationship of differentially expressed miRNAs (left) and mRNAs involved in the adipocytokine signaling pathway (right, identified by DGE, unpublished data). The expression profile of a miRNA or gene in the brain (HB/AB) and adipose tissue (HA/AA) was calculated by sequence counts (TPM). The red and green colors represent high and low gene expression after comparing the hibernating state vs. the active state. Differentially expressed miRNAs and mRNAs (P≤0.01) during hibernation are linked with red lines; (B) Network of adipocytokine signaling pathway. Red box, predicted target genes of differentially expressed miRNAs that were also identified by DGE; Blue box, predicted target genes of differentially expressed miRNAs, but that were not identified by DGE; Green box, genes identified by DGE.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4526555&req=5

pone.0135064.g004: Co-regulation of miRNAs and target mRNAs in the adipocytokine signaling pathway.(A) Expression pattern and relationship of differentially expressed miRNAs (left) and mRNAs involved in the adipocytokine signaling pathway (right, identified by DGE, unpublished data). The expression profile of a miRNA or gene in the brain (HB/AB) and adipose tissue (HA/AA) was calculated by sequence counts (TPM). The red and green colors represent high and low gene expression after comparing the hibernating state vs. the active state. Differentially expressed miRNAs and mRNAs (P≤0.01) during hibernation are linked with red lines; (B) Network of adipocytokine signaling pathway. Red box, predicted target genes of differentially expressed miRNAs that were also identified by DGE; Blue box, predicted target genes of differentially expressed miRNAs, but that were not identified by DGE; Green box, genes identified by DGE.
Mentions: We further examined the adipocytokine signaling pathway to determine the relationship between miRNAs and target mRNAs during hibernation, as adipocytokine signaling is co-regulated by both brain and adipose tissues. Moreover, we searched for mRNAs from our on-going project of digital gene expression (DGE) sequencing to enrich for target genes. DGE sequencing has been conducted on the same animals used here (unpublished data). A total of 64 mRNAs involved in adipocytokine signaling pathway were identified by DGE sequencing (S10 Table, DGE unpublished data). By combining the miRNA and target mRNA expression patterns, we found that 41 of 49 differentially expressed miRNAs regulated the expression of 51 genes, and more than half of the genes in each tissue were up-regulated during hibernation. Among these, the differential expression of three mRNAs (Insulin Receptor Substrate, IRS; Adenosine 5‘-monophosphate (AMP)-activated protein kinase, AMPK; Retinoid X receptor, RXR) was significant (P≤0.01), including IRS over-expression. The others were down-regulated during HA/AA (Fig 4 and S10 Table).

Bottom Line: 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).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.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.

View Article: PubMed Central - PubMed

Affiliation: Guangdong Entomological Institute, Guangzhou, China; Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangzhou, China; Guangdong Key Laboratory of Integrated Pest Management in Agriculture, Guangzhou, China.

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.

No MeSH data available.


Related in: MedlinePlus