Post-transcriptional circadian regulation in macrophages organizes temporally distinct immunometabolic states.

Autor:	Collins EJ; Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, New York 12180, USA., Cervantes-Silva MP; School of Pharmacy and Biomedical Sciences and Tissue Engineering Research Group, Royal College of Surgeons in Ireland, Dublin D02, Ireland., Timmons GA; School of Pharmacy and Biomedical Sciences and Tissue Engineering Research Group, Royal College of Surgeons in Ireland, Dublin D02, Ireland., O'Siorain JR; School of Pharmacy and Biomedical Sciences and Tissue Engineering Research Group, Royal College of Surgeons in Ireland, Dublin D02, Ireland., Curtis AM; School of Pharmacy and Biomedical Sciences and Tissue Engineering Research Group, Royal College of Surgeons in Ireland, Dublin D02, Ireland., Hurley JM; Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.; Center for Biotechnology and Interdisciplinary Sciences, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
Jazyk:	angličtina
Zdroj:	Genome research [Genome Res] 2021 Feb; Vol. 31 (2), pp. 171-185. Date of Electronic Publication: 2021 Jan 12.
DOI:	10.1101/gr.263814.120
Abstrakt:	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. (© 2021 Collins et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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