{"doi":"10.1101/gr.263814.120","title":"Post-transcriptional circadian regulation in macrophages organizes temporally distinct immunometabolic states","abstract":"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.","journal":"Genome Research","year":2021,"id":212812,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":104,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":558160,"name":"Mariana P. Cervantes‐Silva","orcid":null,"position":1,"is_corresponding":false},{"id":558161,"name":"George A. Timmons","orcid":null,"position":2,"is_corresponding":false},{"id":557292,"name":"James R. O’Siorain","orcid":"0000-0003-1064-8292","position":3,"is_corresponding":false},{"id":557293,"name":"Annie M. Curtis","orcid":"0000-0002-9601-9624","position":4,"is_corresponding":false},{"id":322748,"name":"Jennifer Hurley","orcid":"0000-0002-1085-9391","position":5,"is_corresponding":false},{"id":450620,"name":"Emily Collins","orcid":null,"position":0,"is_corresponding":true}],"reference_count":100,"raw_metadata":null,"created_at":"2026-07-18T23:52:31.378994Z","pmid":"33436377","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}