Dynamic RNA Regulation in the Brain Underlies Physiological Plasticity in a Hibernating Mammal

Fu, Rui; Gillen, Austin E.; Grabek, Katharine R.; Riemondy, Kent; Epperson, L. Elaine; Bustamante, Carlos D.; Hesselberth, Jay R.; Martin, Sandra L.

doi:10.3389/fphys.2020.624677

Cited by 11 publications

(48 citation statements)

References 90 publications

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“…Many of the higher fold changes across the pairwise transitions are also MIR_containing, i.e., the longer primary RNA precursors of functional miRNAs: all of these decrease across the torpor bout (Figure 2E). Similar to brain (Fu et al, 2021), transcripts increased in the cold (i.e., higher in Ar than either Ent or IBA) were also biased for higher GC content, as were transcripts elevated in IBA compared to SpD (Figure 2F).…”

Section: Rna-seq Data Analysismentioning

confidence: 91%

“…closer inspection of individual genes revealed many exhibited gene expression dynamics inconsistent with their WGCNA assignments (see also, Botía et al, 2017;Fu et al, 2021), we defined 14 most-common DE patterns in the data and reassigned the 3,120 DE genes to their best-fit cluster. This process placed 95.8% of the DE genes into one of 14 dynamic patterns (Figure 3A and Supplementary Figure 2).…”

Section: Rna-seq Data Analysismentioning

confidence: 99%

“…After adapter removal, quality trimming and a length filter, 14.9 ± 3.4 million reads/sample remained; of these, 10.2 ± 2.2 million reads/sample aligned to the HiC genome (Supplementary Table 1). Initially, we quantified these reads using the same transcript annotation (Fu et al, 2021) as used for the liver RNA-seq analysis described above. Because previous studies of torpid hibernators had demonstrated depressed transcription at low Tb, we were astonished to find large numbers of DE genes that increased in ET compared to Ent, LT compared to ET, or LT compared to IBA (e.g., Nxph4 in Figures 4A,B; Supplementary Figure 3A).…”

Section: Gro-seq Data Analysismentioning

confidence: 99%

“…In addition, reads were mapped to a greatly enhanced ground squirrel genome and annotation for quantification. The genome approaches chromosome-level integrity and includes 42,881 previously identified, newly annotated and novel genes (Fu et al, 2021). We further assess the role of transcriptional control in determining the observed differential gene expression using GRO-seq data (Core et al, 2008), collected for the first time from a hibernator.…”

Section: Introductionmentioning

confidence: 99%

“…Taken together these two datasets demonstrate that transcriptional control dominates the seasonal gene expression changes, while both transcriptional and post-transcriptional mechanisms are clearly involved in gene expression dynamics across the torporarousal cycle. The RNA-seq data were further analyzed for A-to-I RNA editing and differential splicing, both previously shown to occur in brain (Riemondy et al, 2018;Fu et al, 2021), demonstrating that both cold-associated ADAR-mediated RNA editing and differential splicing also occur in liver. As in brain (Fu et al, 2021), these liver data demonstrate the necessity and value of carefully timed samples for use in this type of hibernation study and provide both a resource and a roadmap to guide future work.…”

Section: Introductionmentioning

confidence: 99%

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Liver Transcriptome Dynamics During Hibernation Are Shaped by a Shifting Balance Between Transcription and RNA Stability

Gillen

Riemondy

et al. 2021

Front. Physiol.

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Hibernators dramatically lower metabolism to save energy while fasting for months. Prolonged fasting challenges metabolic homeostasis, yet small-bodied hibernators emerge each spring ready to resume all aspects of active life, including immediate reproduction. The liver is the body’s metabolic hub, processing and detoxifying macromolecules to provide essential fuels to brain, muscle and other organs throughout the body. Here we quantify changes in liver gene expression across several distinct physiological states of hibernation in 13-lined ground squirrels, using RNA-seq to measure the steady-state transcriptome and GRO-seq to measure transcription for the first time in a hibernator. Our data capture key timepoints in both the seasonal and torpor-arousal cycles of hibernation. Strong positive correlation between transcription and the transcriptome indicates that transcriptional control dominates the known seasonal reprogramming of metabolic gene expression in liver for hibernation. During the torpor-arousal cycle, however, discordance develops between transcription and the steady-state transcriptome by at least two mechanisms: 1) although not transcribed during torpor, some transcripts are unusually stable across the torpor bout; and 2) unexpectedly, on some genes, our data suggest continuing, slow elongation with a failure to terminate transcription across the torpor bout. While the steady-state RNAs corresponding to these read through transcripts did not increase during torpor, they did increase shortly after rewarming despite their simultaneously low transcription. Both of these mechanisms would assure the immediate availability of functional transcripts upon rewarming. Integration of transcriptional, post-transcriptional and RNA stability control mechanisms, all demonstrated in these data, likely initiate a serial gene expression program across the short euthermic period that restores the tissue and prepares the animal for the next bout of torpor.

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Section: Rna-seq Data Analysismentioning

confidence: 91%

Section: Rna-seq Data Analysismentioning

confidence: 99%

Section: Gro-seq Data Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Liver Transcriptome Dynamics During Hibernation Are Shaped by a Shifting Balance Between Transcription and RNA Stability

Gillen

Riemondy

et al. 2021

Front. Physiol.

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Comparative transcriptomics of the Djungarian hamster hypothalamus during short photoperiod acclimation and spontaneous torpor

Haugg¹,

Borner

Diedrich³

et al. 2021

FEBS Open Bio

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Djungarian hamsters (Phodopus sungorus, Cricetidae) are photoperiodic mammals [1,2]. In summer or summer-like long photoperiod (LP; e.g., 16:8 light:darkness), they have a high body mass, body temperature, and activity level. They are reproductively active and camouflaged to their environment by a light Abbreviations HT, hypothermia; log2(FC), logarithm of fold change to the base 2; LP, summer-like long photoperiod; NT, normothermia; padj, adjusted ?P-value; SP, winter-like short photoperiod; Tb, core body temperature; ZT, Zeitgeber-time.

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Comparative transcriptomics of the garden dormouse hypothalamus during hibernation

Haugg,

Borner,

Stalder

et al. 2023

FEBS Open Bio

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Torpor or heterothermy is an energy saving mechanism used by endotherms to overcome harsh environmental conditions. During winter, the garden dormouse (Eliomys quercinus) hibernates with multiday torpor bouts and body temperatures of a few degrees Celsius, interrupted by brief euthermic phases. This study investigates gene expression within the hypothalamus, the key brain area controlling energy balance, adding information on differential gene expression potentially relevant to orchestrate torpor. A de novo assembled transcriptome of the hypothalamus was generated from garden dormice hibernating under constant darkness without food and water at 5 °C. Samples were collected during early torpor, late torpor, and interbout arousal. During early torpor, 765 genes were differentially expressed as compared with interbout arousal. Twenty‐seven pathways were over‐represented, including pathways related to hemostasis, extracellular matrix organization and signaling of small molecules. Only 82 genes were found to be differentially expressed between early and late torpor, and no pathways were over‐represented. During late torpor, 924 genes were differentially expressed relative to interbout arousal. Despite the high number of differentially expressed genes, only 10 pathways were over‐represented. Of these, eight were also observed to be over‐represented when comparing early torpor and interbout arousal. Our results are largely consistent with previous findings in other heterotherms. The addition of a transcriptome of a novel species may help to identify species‐specific and overarching torpor mechanisms through future species comparisons.

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Dynamic RNA Regulation in the Brain Underlies Physiological Plasticity in a Hibernating Mammal

Cited by 11 publications

References 90 publications

Liver Transcriptome Dynamics During Hibernation Are Shaped by a Shifting Balance Between Transcription and RNA Stability

Liver Transcriptome Dynamics During Hibernation Are Shaped by a Shifting Balance Between Transcription and RNA Stability

Comparative transcriptomics of the Djungarian hamster hypothalamus during short photoperiod acclimation and spontaneous torpor

Comparative transcriptomics of the garden dormouse hypothalamus during hibernation

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