期刊
GENOME RESEARCH
卷 31, 期 2, 页码 -出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.263814.120
关键词
-
资金
- National Institutes of Health, National Institute of General Medical Sciences [T32GM067545, GM128687]
- Rensselaer startup funds
- Consejo Nacional de Ciencia y Tecnologia [CVU440823]
- Science Foundation Ireland Career Development Award [17/CDA/4688]
- Irish Research Council Laureate Award [IRCLA/2017/110]
- Irish Research Council (IRC) [IRCLA/2017/110] Funding Source: Irish Research Council (IRC)
The circadian clock plays a crucial role in immunity, with post-transcriptional regulation influencing macrophage clock regulatory output significantly, particularly in metabolic pathways. Daily variations in metabolic pathways, ATP production, mitochondrial morphology, and phagocytosis correspond to post-transcriptional temporal-gating and are essential for determining the response of macrophages to immune stimuli.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据