title: Enhanced stability and polyadenylation of select mRNAs support rapid thermogenesis in the brown fat of a hibernator.
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.
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, United States.
authors.forename: Katharine R
authors.initials: KR
authors.lastname: Grabek
authors.affiliation: Department of Applied Math and Statistics, Colorado School of Mines, Golden, United States.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Diniz Behn
authors.affiliation: Department of Research, HudsonAlpha Institute for Biotechnology, Huntsville, United States.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Barsh
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, United States.
authors.forename: Jay R
authors.initials: JR
authors.lastname: Hesselberth
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, United States.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Martin
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001143:Arousal / Q000502:physiology; D001483:Base Sequence; D001831:Body Temperature / Q000502:physiology; D015723:Gene Library; D006605:Hibernation / Q000235:genetics*; D008954:Models, Biological; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs / Q000235:genetics; D010641:Phenotype; D026723:Polyadenylation / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012589:Sciuridae / Q000235:genetics; D012984:Software; D022722:Thermogenesis / Q000235:genetics*
chemical_list: D012333:RNA, Messenger
keywords: Ictidomys tridecemlineatus; biological oscillation; digital transcriptome; evolutionary biology; genomics; non-shivering thermogenesis