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

Grabek KR, Diniz Behn C, Barsh GS, Hesselberth JR, Martin SL - Elife (2015)

Bottom Line: A cohort of transcripts increased during torpor, paradoxical because transcription effectively ceases at these low temperatures.We show that this increase occurs not by elevated transcription but rather by enhanced stabilization associated with maintenance and/or extension of long poly(A) tails.This subset was enriched in a C-rich motif and genes required for BAT activation, suggesting a model and mechanism to prioritize translation of key proteins for thermogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, United States.

ABSTRACT
During hibernation, animals cycle between torpor and arousal. These cycles involve dramatic but poorly understood mechanisms of dynamic physiological regulation at the level of gene expression. Each cycle, Brown Adipose Tissue (BAT) drives periodic arousal from torpor by generating essential heat. We applied digital transcriptome analysis to precisely timed samples to identify molecular pathways that underlie the intense activity cycles of hibernator BAT. A cohort of transcripts increased during torpor, paradoxical because transcription effectively ceases at these low temperatures. We show that this increase occurs not by elevated transcription but rather by enhanced stabilization associated with maintenance and/or extension of long poly(A) tails. Mathematical modeling further supports a temperature-sensitive mechanism to protect a subset of transcripts from ongoing bulk degradation instead of increased transcription. This subset was enriched in a C-rich motif and genes required for BAT activation, suggesting a model and mechanism to prioritize translation of key proteins for thermogenesis.

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The hibernating phenotype as a model for studying BAT metabolicregulation.(A) Schematic depicting the metabolic suppression and activationcycle of BAT during the highly recruited, winter hibernation phase (blueshading) of the annual cycle. Cartoon squirrels represent general phenotypicchanges among annual and torpor–arousal cycles (Hindle and Martin, 2014). (B) Relationshipof sample groups to body temperature over time. Blue highlighting on monthsindicates hibernation.DOI:http://dx.doi.org/10.7554/eLife.04517.003
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fig1: The hibernating phenotype as a model for studying BAT metabolicregulation.(A) Schematic depicting the metabolic suppression and activationcycle of BAT during the highly recruited, winter hibernation phase (blueshading) of the annual cycle. Cartoon squirrels represent general phenotypicchanges among annual and torpor–arousal cycles (Hindle and Martin, 2014). (B) Relationshipof sample groups to body temperature over time. Blue highlighting on monthsindicates hibernation.DOI:http://dx.doi.org/10.7554/eLife.04517.003

Mentions: Many mammals hibernate to conserve energy during extended periods of limited resourceavailability and harsh environmental conditions. As winter approaches in temperateclimates, hibernators enter into a state of torpor. Torpor in ground squirrels involvesactive suppression of physiological processes to 2–5% of basal rates, whichallows body temperature to lower to just above ambient, even as ambient temperaturesfall to near freezing. This depressed state is not continuous throughout winter,however, instead it lasts for 1–3 weeks until it is punctuated by a spontaneous,rapid re-warming to 37°C; physiological rates during re-warming match or evenexceed basal rates. The interbout arousal period is then sustained for 12–24 hrbefore torpor resumes. Cycles between torpor and arousal result in winter heterothermyor hibernation (Figure 1). Hibernation persistsfor 5–8 months before emergence in spring and maintenance of more typicalmammalian homeostatic physiology throughout the summer period of growth and reproduction(Figure 1, see Carey et al., 2003; for review). Although of broad medicalinterest for their ability to tolerate these extraordinary physiological extremes (Carey et al., 2003; Andrews, 2007; Carey et al.,2012; Dave et al., 2012), manyaspects of the hibernation phenotype remain poorly understood. Some of hibernation'smost defining mysteries are the mechanisms that underlie the highly dynamic oscillationsof the torpor–arousal cycle.10.7554/eLife.04517.003Figure 1.The hibernating phenotype as a model for studying BAT metabolicregulation.


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

Grabek KR, Diniz Behn C, Barsh GS, Hesselberth JR, Martin SL - Elife (2015)

The hibernating phenotype as a model for studying BAT metabolicregulation.(A) Schematic depicting the metabolic suppression and activationcycle of BAT during the highly recruited, winter hibernation phase (blueshading) of the annual cycle. Cartoon squirrels represent general phenotypicchanges among annual and torpor–arousal cycles (Hindle and Martin, 2014). (B) Relationshipof sample groups to body temperature over time. Blue highlighting on monthsindicates hibernation.DOI:http://dx.doi.org/10.7554/eLife.04517.003
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383249&req=5

fig1: The hibernating phenotype as a model for studying BAT metabolicregulation.(A) Schematic depicting the metabolic suppression and activationcycle of BAT during the highly recruited, winter hibernation phase (blueshading) of the annual cycle. Cartoon squirrels represent general phenotypicchanges among annual and torpor–arousal cycles (Hindle and Martin, 2014). (B) Relationshipof sample groups to body temperature over time. Blue highlighting on monthsindicates hibernation.DOI:http://dx.doi.org/10.7554/eLife.04517.003
Mentions: Many mammals hibernate to conserve energy during extended periods of limited resourceavailability and harsh environmental conditions. As winter approaches in temperateclimates, hibernators enter into a state of torpor. Torpor in ground squirrels involvesactive suppression of physiological processes to 2–5% of basal rates, whichallows body temperature to lower to just above ambient, even as ambient temperaturesfall to near freezing. This depressed state is not continuous throughout winter,however, instead it lasts for 1–3 weeks until it is punctuated by a spontaneous,rapid re-warming to 37°C; physiological rates during re-warming match or evenexceed basal rates. The interbout arousal period is then sustained for 12–24 hrbefore torpor resumes. Cycles between torpor and arousal result in winter heterothermyor hibernation (Figure 1). Hibernation persistsfor 5–8 months before emergence in spring and maintenance of more typicalmammalian homeostatic physiology throughout the summer period of growth and reproduction(Figure 1, see Carey et al., 2003; for review). Although of broad medicalinterest for their ability to tolerate these extraordinary physiological extremes (Carey et al., 2003; Andrews, 2007; Carey et al.,2012; Dave et al., 2012), manyaspects of the hibernation phenotype remain poorly understood. Some of hibernation'smost defining mysteries are the mechanisms that underlie the highly dynamic oscillationsof the torpor–arousal cycle.10.7554/eLife.04517.003Figure 1.The hibernating phenotype as a model for studying BAT metabolicregulation.

Bottom Line: A cohort of transcripts increased during torpor, paradoxical because transcription effectively ceases at these low temperatures.We show that this increase occurs not by elevated transcription but rather by enhanced stabilization associated with maintenance and/or extension of long poly(A) tails.This subset was enriched in a C-rich motif and genes required for BAT activation, suggesting a model and mechanism to prioritize translation of key proteins for thermogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, United States.

ABSTRACT
During hibernation, animals cycle between torpor and arousal. These cycles involve dramatic but poorly understood mechanisms of dynamic physiological regulation at the level of gene expression. Each cycle, Brown Adipose Tissue (BAT) drives periodic arousal from torpor by generating essential heat. We applied digital transcriptome analysis to precisely timed samples to identify molecular pathways that underlie the intense activity cycles of hibernator BAT. A cohort of transcripts increased during torpor, paradoxical because transcription effectively ceases at these low temperatures. We show that this increase occurs not by elevated transcription but rather by enhanced stabilization associated with maintenance and/or extension of long poly(A) tails. Mathematical modeling further supports a temperature-sensitive mechanism to protect a subset of transcripts from ongoing bulk degradation instead of increased transcription. This subset was enriched in a C-rich motif and genes required for BAT activation, suggesting a model and mechanism to prioritize translation of key proteins for thermogenesis.

Show MeSH
Related in: MedlinePlus