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

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. W...

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Autores principales: Grabek, Katharine R, Diniz Behn, Cecilia, Barsh, Gregory S, Hesselberth, Jay R, Martin, Sandra L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383249/
https://www.ncbi.nlm.nih.gov/pubmed/25626169
http://dx.doi.org/10.7554/eLife.04517
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author Grabek, Katharine R
Diniz Behn, Cecilia
Barsh, Gregory S
Hesselberth, Jay R
Martin, Sandra L
author_facet Grabek, Katharine R
Diniz Behn, Cecilia
Barsh, Gregory S
Hesselberth, Jay R
Martin, Sandra L
author_sort Grabek, Katharine R
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.04517.001
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spelling pubmed-43832492015-04-03 Enhanced stability and polyadenylation of select mRNAs support rapid thermogenesis in the brown fat of a hibernator Grabek, Katharine R Diniz Behn, Cecilia Barsh, Gregory S Hesselberth, Jay R Martin, Sandra L eLife Genomics and Evolutionary Biology 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. DOI: http://dx.doi.org/10.7554/eLife.04517.001 eLife Sciences Publications, Ltd 2015-01-27 /pmc/articles/PMC4383249/ /pubmed/25626169 http://dx.doi.org/10.7554/eLife.04517 Text en © 2014, Grabek et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Genomics and Evolutionary Biology
Grabek, Katharine R
Diniz Behn, Cecilia
Barsh, Gregory S
Hesselberth, Jay R
Martin, Sandra L
Enhanced stability and polyadenylation of select mRNAs support rapid thermogenesis in the brown fat of a hibernator
title Enhanced stability and polyadenylation of select mRNAs support rapid thermogenesis in the brown fat of a hibernator
title_full Enhanced stability and polyadenylation of select mRNAs support rapid thermogenesis in the brown fat of a hibernator
title_fullStr Enhanced stability and polyadenylation of select mRNAs support rapid thermogenesis in the brown fat of a hibernator
title_full_unstemmed Enhanced stability and polyadenylation of select mRNAs support rapid thermogenesis in the brown fat of a hibernator
title_short Enhanced stability and polyadenylation of select mRNAs support rapid thermogenesis in the brown fat of a hibernator
title_sort enhanced stability and polyadenylation of select mrnas support rapid thermogenesis in the brown fat of a hibernator
topic Genomics and Evolutionary Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383249/
https://www.ncbi.nlm.nih.gov/pubmed/25626169
http://dx.doi.org/10.7554/eLife.04517
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