Post-transcriptional circadian regulation in macrophages organizes temporally distinct immunometabolic states.
Post-transcriptional circadian regulation in macrophages organizes temporally distinct immunometabolic states.
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巨噬细胞转录后昼夜节律调节组织时间上不同的免疫代谢状态。
DOI：
10.1101/gr.263814.120
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发表时间：
2021-03
期刊：
影响因子：
7
通讯作者：
Hurley JM
中科院分区：
文献类型：
--
作者：
Collins EJ;Cervantes-Silva MP;Timmons GA;O'Siorain JR;Curtis AM;Hurley JM
我们的核心计时机制，生物钟，在免疫中起着至关重要的作用。尽管生物钟对免疫反应的昼夜节律控制机制通常是通过转录激活或抑制来解释的，但研究表明，一些调节发生在转录活动之外。我们全面分析了小鼠骨髓来源的巨噬细胞的转录组和蛋白质组，发现只有15%的昼夜蛋白质组有相应的振荡mRNA，这表明转录后调控对巨噬细胞时钟调节输出的影响比之前分析的任何其他组织都要大。这一调节可能是因为我们发现参与降解和翻译的蛋白质在时间上的强健富集性。广泛的转录后时间门控代谢途径也被观察到，并进一步与ATP生产、线粒体形态和吞噬作用的每日变化相对应。这种昼夜节律转录后代谢调节的破坏会损害免疫功能。我们的结果表明，细胞固有的转录后调控是巨噬细胞昼夜节律输出的主要驱动因素，这种调控，特别是代谢途径的调控，在决定巨噬细胞对免疫刺激的反应中发挥着重要作用。
Our core timekeeping mechanism, the circadian clock, plays a vital role in immunity. Although the mechanics of circadian control over the immune response is generally explained by transcriptional activation or repression derived from this clock's transcription-translation negative-feedback loop, research suggests that some regulation occurs beyond transcriptional activity. We comprehensively profiled the transcriptome and proteome of murine bone marrow-derived macrophages and found that only 15% of the circadian proteome had corresponding oscillating mRNA, suggesting post-transcriptional regulation influences macrophage clock regulatory output to a greater extent than any other tissue previously profiled. This regulation may be explained by the robust temporal enrichment we identified for proteins involved in degradation and translation. Extensive post-transcriptional temporal-gating of metabolic pathways was also observed and further corresponded with daily variations in ATP production, mitochondrial morphology, and phagocytosis. The disruption of this circadian post-transcriptional metabolic regulation impaired immune functionality. Our results demonstrate that cell-intrinsic post-transcriptional regulation is a primary driver of circadian output in macrophages and that this regulation, particularly of metabolic pathways, plays an important role in determining their response to immune stimuli.
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影响因子：
2.8
作者：
Cermakian N;Lange T;Golombek D;Sarkar D;Nakao A;Shibata S;Mazzoccoli G
通讯作者：
Mazzoccoli G
DOI：
10.1073/pnas.1525268113
发表时间：
2016-08-23
影响因子：
11.1
作者：
Caster, Stephen Z.;Castillo, Kathrina;Bell-Pedersen, Deborah
通讯作者：
Bell-Pedersen, Deborah
影响因子：
64.5
作者：
Balsalobre, A;Damiola, F;Schibler, U
通讯作者：
Schibler, U
DOI：
10.1073/pnas.1800431115
发表时间：
2018-09-04
影响因子：
11.1
作者：
Early JO;Menon D;Wyse CA;Cervantes-Silva MP;Zaslona Z;Carroll RG;Palsson-McDermott EM;Angiari S;Ryan DG;Corcoran SE;Timmons G;Geiger SS;Fitzpatrick DJ;O'Connell D;Xavier RJ;Hokamp K;O'Neill LAJ;Curtis AM
通讯作者：
Curtis AM
影响因子：
7.3
作者：
Angajala A;Lim S;Phillips JB;Kim JH;Yates C;You Z;Tan M
通讯作者：
Tan M