{"doi":"10.1101/2024.12.19.628772","title":"Post-transcriptional modifications on tRNA fragments confer functional changes to high-density lipoproteins in atherosclerosis","abstract":"SUMMARY Epitranscriptomic modifications on RNA play critical roles in stability, processing, and function, partly by influencing interactions with RNA-binding proteins and receptors. The role of post-transcriptional RNA modifications on cell-free non-coding small RNA (sRNA) remains poorly understood in disease contexts. High-density lipoproteins (HDL), which transport sRNAs, can lose their beneficial properties in atherosclerosis cardiovascular disease (ASCVD). We hypothesize that changes to regulatory modifications on HDL-sRNAs contribute to this dysfunction. To assess changes in HDL-sRNA modification status, HDL-derived RNA from healthy subjects and those with atherosclerotic lesion development were analyzed using LC-MS/MS and AlkB-facilitated RNA (de)Methylation Sequencing. ASVD-HDL showed an enrichment in modified nucleosides including m 1 A tRNA-derived sRNAs (tDRs), particularly tDR-ArgACG-1. Functional studies revealed that ASCVD-HDL induced cell adhesion genes, including TMEM123, in primary macrophages. Recombinant HDL loaded with m 1 A-tDR-ArgACG-1 induced immune signaling, and similarly upregulated TMEM123. These findings suggest HDL-delivered-m 1 A-tDR-ArgACG-1 act on adhesion genes and immune pathways, promoting macrophage activation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":492712,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.946,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":477702,"name":"Danielle L. Michell","orcid":"0000-0002-2048-4191","position":1,"is_corresponding":false},{"id":390887,"name":"Philip J. Kingsley","orcid":"0000-0002-5470-4340","position":2,"is_corresponding":false},{"id":955159,"name":"Clark Massick","orcid":"0009-0009-4418-2006","position":3,"is_corresponding":false},{"id":619368,"name":"Marisol Ramirez","orcid":null,"position":4,"is_corresponding":false},{"id":820090,"name":"Mark Castleberry","orcid":"0000-0002-7916-5451","position":5,"is_corresponding":false},{"id":16597,"name":"Amanda C. Doran","orcid":"0000-0002-1576-6274","position":6,"is_corresponding":false},{"id":262998,"name":"J. Jeffrey Carr","orcid":"0000-0002-4398-8237","position":7,"is_corresponding":false},{"id":318552,"name":"Lawrence J. Marnett","orcid":"0000-0002-7834-6285","position":8,"is_corresponding":false},{"id":86835,"name":"Quanhu Sheng","orcid":"0000-0001-8951-9295","position":9,"is_corresponding":false},{"id":341987,"name":"MacRae F. Linton","orcid":"0000-0002-9277-0453","position":10,"is_corresponding":false},{"id":477703,"name":"Kasey C. Vickers","orcid":"0000-0001-5643-3102","position":11,"is_corresponding":false},{"id":820089,"name":"Elizabeth M. Semler","orcid":"0000-0002-0271-2728","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:56.210382Z","pmid":"39763941","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":[]}