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| Status |
Public on May 10, 2021 |
| Title |
Liver transcriptome dynamics during hibernation are shaped by a shifting balance between transcription and RNA stability |
| Organism |
Ictidomys tridecemlineatus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
RNA-seq libraries were prepared from replicate samples (n=5) from five physiolocial groups to capture key changes in circannual hibernation plus one extra liver sequenced more deeply for annotation purposes only (L200); 26 samples total
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| Contributor(s) |
Martin SL |
| Citation(s) |
34093224 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 HL089049 |
Biomarkers for the two phase switches of mammalian hibernation |
UNIVERSITY OF COLORADO DENVER |
SANDRA L MARTIN |
| R01 DK043806 |
Integrative Physiology of Thyroid Hormone Receptors and Nuclear Receptor Corepressors |
UNIVERSITY OF PENNSYLVANIA |
MITCHELL A. LAZAR |
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| |
| Submission date |
Feb 16, 2021 |
| Last update date |
Jun 09, 2021 |
| Contact name |
Sandy Martin |
| E-mail(s) |
[email protected]
|
| Organization name |
University of Colorado School of Medicine
|
| Department |
Cell and Developmental Biology
|
| Street address |
12801 E. 17th Ave.
|
| City |
Aurora |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24271 |
Illumina HiSeq 4000 (Ictidomys tridecemlineatus) |
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| Samples (26)
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| Relations |
| BioProject |
PRJNA702062 |
| SRA |
SRP306578 |
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