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. 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...在冬眠过程中，动物会在蛰伏(torpor)与觉醒(arousal)之间循环往复。这类循环涉及机体在基因表达层面上极为显著但尚未完全阐明的动态生理调控机制。在每个循环中，棕色脂肪组织(Brown Adipose Tissue, BAT)通过产生必需热量，驱动动物从蛰伏状态周期性觉醒。本研究对精准计时的样本开展数字转录组分析，以揭示冬眠动物棕色脂肪组织剧烈活性循环背后的分子通路。研究发现，有一类转录本在蛰伏阶段的表达量升高，这一现象看似矛盾：因为在这类低温环境下，转录过程实际上已基本停止。本研究证实，这类转录本的表达量上升并非源于转录水平升高，而是得益于与长多聚腺苷酸尾(poly(A) tails)的维持和/或延长相关的稳定性增强。数学建模进一步佐证了一种温度敏感型机制：该机制可保护特定子集的转录本免受持续的整体降解，而非通过提升转录水平实现表达量上调。该转录本子集富含胞嘧啶富集基序(C-rich motif)，以及棕色脂肪组织功能所需的相关基因……