Liver transcriptome dynamics during hibernation are shaped by a shifting balance between transcription and RNA stability
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ABSTRACT:
PROVIDER: PRJNA702062 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13718900_1.fastq.gz | Fastqsanger.gz | |||
| SRR13718900_2.fastq.gz | Fastqsanger.gz | |||
| SRR13718901_1.fastq.gz | Fastqsanger.gz | |||
| SRR13718901_2.fastq.gz | Fastqsanger.gz | |||
| SRR13718902_1.fastq.gz | Fastqsanger.gz |
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Project description: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, we document continuing, slow elongation with a failure to terminate transcription across the torpor bout. While the steady-state RNAs corresponding to these readthrough 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.
2021-05-10 | GSE166814 | GEO
Project description: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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Project description:Mammalian hibernators display phenotypes similar to physiological conditions in non-hibernating species under conditions of calorie restriction and fasting, hypoxia, hypothermia, ischemia-reperfusion, and sleep. However, whether or how similarities are also reflected on molecular and genetic levels is unclear. We identified molecular signatures of torpor and arousal in hibernation using a new custom-designed cDNA microarray for the arctic ground squirrel (Urocitellus parryii,) and compared them to molecular signatures of selected phenotypes in mouse. Our results show that differential gene expression related to metabolism during torpor is closely related to that during calorie restriction and hypoxia. PPARM-NM-1 is crucial for metabolic remodeling in hibernation. Genes related to the sleep-wake cycle and temperature response genes induced by hypothermia follow the same expression changes as in torpor-arousal cycle. Increased fatty acid metabolism might contribute to the protection against ischemia-reperfusion injury during hibernation. Further, by comparing with thousands of pharmacological signatures, we identified drugs that may induce similar expression patterns in human cell lines as during hibernation. Arctic ground squirrels sampled during winter hibernation were compared with the animals sampled during summer. Liver was hybridized on a custom 9,600 probes nylon membrane microarray platform. Four squirrels in early torpor, five in late torpor, four in early arousal, four in late arousal, and seven in summer active were studied in experiments.
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Project description:Hibernation is a complex physiological state often exploited by animals under adverse environmental conditions. It involves large changes in metabolism and cellular function, with many stress responses modulated to tolerate physiological challenges that would otherwise be lethal. This study explores transcriptomic and proteomic profiling of hibernation in a reptile (the central bearded dragon; Pogona vitticeps) throughout the hibernation season. To better understand molecular dynamics of this remarkable process, total RNA and protein was analyzed in brain, heart and skeletal muscle at three time points; late hibernation, two days post-arousal, and two months post-arousal.
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