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

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,...

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Autores principales: Gillen, Austin E., Fu, Rui, Riemondy, Kent A., Jager, Jennifer, Fang, Bin, Lazar, Mitchell A., Martin, Sandra L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176218/
https://www.ncbi.nlm.nih.gov/pubmed/34093224
http://dx.doi.org/10.3389/fphys.2021.662132
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author Gillen, Austin E.
Fu, Rui
Riemondy, Kent A.
Jager, Jennifer
Fang, Bin
Lazar, Mitchell A.
Martin, Sandra L.
author_facet Gillen, Austin E.
Fu, Rui
Riemondy, Kent A.
Jager, Jennifer
Fang, Bin
Lazar, Mitchell A.
Martin, Sandra L.
author_sort Gillen, Austin E.
collection PubMed
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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spelling pubmed-81762182021-06-05 Liver Transcriptome Dynamics During Hibernation Are Shaped by a Shifting Balance Between Transcription and RNA Stability Gillen, Austin E. Fu, Rui Riemondy, Kent A. Jager, Jennifer Fang, Bin Lazar, Mitchell A. Martin, Sandra L. Front Physiol Physiology 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. Frontiers Media S.A. 2021-05-21 /pmc/articles/PMC8176218/ /pubmed/34093224 http://dx.doi.org/10.3389/fphys.2021.662132 Text en Copyright © 2021 Gillen, Fu, Riemondy, Jager, Fang, Lazar and Martin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Gillen, Austin E.
Fu, Rui
Riemondy, Kent A.
Jager, Jennifer
Fang, Bin
Lazar, Mitchell A.
Martin, Sandra L.
Liver Transcriptome Dynamics During Hibernation Are Shaped by a Shifting Balance Between Transcription and RNA Stability
title Liver Transcriptome Dynamics During Hibernation Are Shaped by a Shifting Balance Between Transcription and RNA Stability
title_full Liver Transcriptome Dynamics During Hibernation Are Shaped by a Shifting Balance Between Transcription and RNA Stability
title_fullStr Liver Transcriptome Dynamics During Hibernation Are Shaped by a Shifting Balance Between Transcription and RNA Stability
title_full_unstemmed Liver Transcriptome Dynamics During Hibernation Are Shaped by a Shifting Balance Between Transcription and RNA Stability
title_short Liver Transcriptome Dynamics During Hibernation Are Shaped by a Shifting Balance Between Transcription and RNA Stability
title_sort liver transcriptome dynamics during hibernation are shaped by a shifting balance between transcription and rna stability
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176218/
https://www.ncbi.nlm.nih.gov/pubmed/34093224
http://dx.doi.org/10.3389/fphys.2021.662132
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