Enhanced stability and polyadenylation of select mRNAs support rapid thermogenesis in the brown fat of a hibernator

Grabek, Katharine R.; Behn, Cecilia Diniz; Barsh, Gregory S.; Hesselberth, Jay R.; Martin, Sandra L.

doi:10.7554/elife.04517

Cited by 33 publications

(44 citation statements)

References 61 publications

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“…The pattern of host gene expression we observed indicates that inflammatory responses in locally infected tissue are greatly elevated during arousals but decline during torpor. The infection‐dependent differences in transcript levels during torpor may indicate that transcripts are being selectively protected from degradation, as transcription is presumably halted during torpor (Grabek, Diniz Behn, et al., ). Increased stabilization of some transcripts during torpor has been proposed to allow translation to occur earlier during subsequent arousals (Bogren et al., ; Grabek, Diniz Behn, et al., ) and would be expected to enhance responses to infection during these arousals.…”

Section: Discussionmentioning

confidence: 99%

Effect of torpor on host transcriptomic responses to a fungal pathogen in hibernating bats

et al. 2018

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Hibernation, the use of prolonged torpor to depress metabolism, is employed by mammals to conserve resources during extended periods of extreme temperatures and/or resource limitation. Mammalian hibernators arouse to euthermy periodically during torpor for reasons that are not well understood, and these arousals may facilitate immune processes. To determine whether arousals enable host responses to pathogens, we used dual RNA-Seq and a paired sampling approach to examine gene expression in a hibernating bat, the little brown myotis (Myotis lucifugus). During torpor, transcript levels differed in only a few genes between uninfected wing tissue and adjacent tissue infected with Pseudogymnoascus destructans, the fungal pathogen that causes white-nose syndrome. Within 70-80 min after emergence from torpor, large changes in gene expression were observed due to local infection, particularly in genes involved in pro-inflammatory host responses to fungal pathogens, but also in many genes involved in immune responses and metabolism. These results support the hypothesis that torpor is a period of relative immune dormancy and arousals allow for local immune responses in infected tissues during hibernation. Host-pathogen interactions were also found to regulate gene expression in the pathogen differently depending on the torpor state of the host. Hibernating species must balance the benefits of energy and water conservation achieved during torpor with the costs of decreased immune competence. Interbout arousals allow hibernators to optimize these, and other, trade-offs during prolonged hibernation by enabling host responses to pathogens within brief, periodic episodes of euthermy.

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Section: Discussionmentioning

confidence: 99%

Effect of torpor on host transcriptomic responses to a fungal pathogen in hibernating bats

et al. 2018

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“…For example, the seasonal increase in adipocytes could lead to an increase in lipid metabolism gene transcription. Transcription (40,94) and translation (31) slow dramatically during torpor, increasing the impact of the stability of the mRNA and proteins (34).…”

Section: Discussionmentioning

confidence: 99%

Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels

Cooper

Sell

Fahrenkrog

et al. 2016

Physiological Genomics

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M. Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels. Physiol Genomics 48: 513-525, 2016. First published May 20, 2016 doi:10.1152/physiolgenomics.00120.2015.-Mammalian hibernators adapt to prolonged periods of immobility, hypometabolism, hypothermia, and oxidative stress, each capable of reducing bone marrow activity. In this study bone marrow transcriptomes were compared among thirteen-lined ground squirrels collected in July, winter torpor, and winter interbout arousal (IBA). The results were consistent with a suppression of acquired immune responses, and a shift to innate immune responses during hibernation through higher complement expression. Consistent with the increase in adipocytes found in bone marrow of hibernators, expression of genes associated with white adipose tissue are higher during hibernation. Genes that should strengthen the bone by increasing extracellular matrix were higher during hibernation, especially the collagen genes. Finally, expression of heat shock proteins were lower, and cold-response genes were higher, during hibernation. No differential expression of hematopoietic genes involved in erythrocyte or megakaryocyte production was observed. This global view of the changes in the bone marrow transcriptome over both short term (torpor vs. IBA) and long term (torpor vs. July) hypothermia can explain several observations made about circulating blood cells and the structure and strength of the bone during hibernation. erythrocyte; leukocyte; megakaryocyte; osteoblast; adipose BONE MARROW IS A COMPLEX ORGAN consisting of many different cell types and stem cell pools. These cells express both unique and common sets of genes and likely influence each other's activities. Hematopoietic stem cells can differentiate into lymphoid progenitor cells that produce natural killer cells and lymphocytes, or into myeloid progenitor cells that give rise to erythrocytes, the remaining leukocytes, and megakaryocytes. Megakaryocytes in turn shed anucleated platelets involved in blood clotting and inflammation. Bone marrow resident mesenchymal stem cells can differentiate to produce resident bone cells including osteoblasts, adipocytes, and chondrocytes (64). Osteoblasts can terminally differentiate into osteocytes and are involved in maintaining bone strength and extracellular matrix production. Bone marrow adipose composition is affected by age, diet, and disease states. Bone marrow may also contain skeletal muscle and hepatocyte stem cell pools. Because of the rapid rate of mitosis by multiple resident stem cell pools, bone marrow is sensitive to damage by radiation and chemotherapy, leaving patients immunocompromised and anemic (25). Bone mineral density and collagen are decreased by prolonged disuse such as bed rest or immobilization (45,86). Recent studies have also demonstrated an increase in neutrophils, natural killer cells, and lymphocytes and a decrease in monocytes in patients subjected to 60 days of bed rest (38). Finally, bone marrow adipocytes increase in ...

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“…a subset of transcripts that increase in relative abundance over the torpor bout, likely owing to selective mRNA stabilization (Grabek et al, 2015a). These transcripts were enriched for gene products that are essential for NST, and they are available for immediate use in the early arousal period whereas some cohorts of transcripts increase during torpor at low T b (Grabek et al, 2015a).…”

Section: Post-transcriptional Regulation Of Batmentioning

confidence: 99%

Section: Post-transcriptional Regulation Of Batmentioning

confidence: 99%

“…These transcripts were enriched for gene products that are essential for NST, and they are available for immediate use in the early arousal period whereas some cohorts of transcripts increase during torpor at low T b (Grabek et al, 2015a). Overall, the cycle of transcription, degradation, stabilization and polyadenylation in BAT leads to translation of the correct transcripts at the precise time with minimal energy costs (Grabek et al, 2015a). This mechanism allows transcripts to be prioritized for immediate translation when BAT activity needs to be quickly resumed (Grabek et al, 2015a), which may suggest possible therapeutic strategies for rapid BAT activation in humans (Grabek et al, 2015a).…”

Section: Post-transcriptional Regulation Of Batmentioning

confidence: 99%

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Nature's fat-burning machine: brown adipose tissue in a hibernating mammal

Ballinger

Andrews

2018

Journal of Experimental Biology

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Brown adipose tissue (BAT) is a unique thermogenic tissue in mammals that rapidly produces heat via nonshivering thermogenesis. Small mammalian hibernators have evolved the greatest capacity for BAT because they use it to rewarm from hypothermic torpor numerous times throughout the hibernation season. Although hibernator BAT physiology has been investigated for decades, recent efforts have been directed toward understanding the molecular underpinnings of BAT regulation and function using a variety of methods, from mitochondrial functional assays to 'omics' approaches. As a result, the inner-workings of hibernator BAT are now being illuminated. In this Review, we discuss recent research progress that has identified players and pathways involved in brown adipocyte differentiation and maturation, as well as those involved in metabolic regulation. The unique phenotype of hibernation, and its reliance on BAT to generate heat to arouse mammals from torpor, has uncovered new molecular mechanisms and potential strategies for biomedical applications.

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Enhanced stability and polyadenylation of select mRNAs support rapid thermogenesis in the brown fat of a hibernator

Cited by 33 publications

References 61 publications

Effect of torpor on host transcriptomic responses to a fungal pathogen in hibernating bats

Effect of torpor on host transcriptomic responses to a fungal pathogen in hibernating bats

Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels

Nature's fat-burning machine: brown adipose tissue in a hibernating mammal

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