{"doi":"10.1038/s41564-024-01638-5","title":"Single-molecule epitranscriptomic analysis of full-length HIV-1 RNAs reveals functional roles of site-specific m6As","abstract":"Abstract Although the significance of chemical modifications on RNA is acknowledged, the evolutionary benefits and specific roles in human immunodeficiency virus (HIV-1) replication remain elusive. Most studies have provided only population-averaged values of modifications for fragmented RNAs at low resolution and have relied on indirect analyses of phenotypic effects by perturbing host effectors. Here we analysed chemical modifications on HIV-1 RNAs at the full-length, single RNA level and nucleotide resolution using direct RNA sequencing methods. Our data reveal an unexpectedly simple HIV-1 modification landscape, highlighting three predominant N 6 -methyladenosine (m 6 A) modifications near the 3′ end. More densely installed in spliced viral messenger RNAs than in genomic RNAs, these m 6 As play a crucial role in maintaining normal levels of HIV-1 RNA splicing and translation. HIV-1 generates diverse RNA subspecies with distinct m 6 A ensembles, and maintaining multiple of these m 6 As on its RNAs provides additional stability and resilience to HIV-1 replication, suggesting an unexplored viral RNA-level evolutionary strategy.","journal":"Nature Microbiology","year":2024,"id":418331,"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":52,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"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":1205829,"name":"Ga-Eun Lee","orcid":"0000-0002-7521-5546","position":1,"is_corresponding":false},{"id":1005567,"name":"Sarah Golconda","orcid":"0000-0001-6398-7285","position":2,"is_corresponding":false},{"id":1196157,"name":"Asif Rayhan","orcid":"0009-0008-4538-6863","position":3,"is_corresponding":false},{"id":1206688,"name":"Anastasios A. Manganaris","orcid":null,"position":4,"is_corresponding":false},{"id":121773,"name":"Shuliang Chen","orcid":"0000-0002-7175-7604","position":5,"is_corresponding":false},{"id":585416,"name":"Nagaraja Tirumuru","orcid":"0000-0001-9042-5210","position":6,"is_corresponding":false},{"id":973928,"name":"Hannah Yu","orcid":"0000-0001-5354-7622","position":7,"is_corresponding":false},{"id":973927,"name":"Shihyoung Kim","orcid":"0000-0002-8846-2853","position":8,"is_corresponding":false},{"id":1206689,"name":"Christopher Kimmel","orcid":null,"position":9,"is_corresponding":false},{"id":109396,"name":"Olivier Zablocki","orcid":"0000-0001-7561-1373","position":10,"is_corresponding":false},{"id":106774,"name":"Matthew B. Sullivan","orcid":"0000-0001-8398-8234","position":12,"is_corresponding":false},{"id":576943,"name":"Li Wu","orcid":"0000-0002-5468-2487","position":13,"is_corresponding":false},{"id":585611,"name":"Sanggu Kim","orcid":"0000-0003-1228-6168","position":14,"is_corresponding":false},{"id":945158,"name":"Alice Baek","orcid":"0000-0002-3631-7988","position":0,"is_corresponding":true}],"reference_count":102,"raw_metadata":null,"created_at":"2026-07-19T01:57:02.483590Z","pmid":"38605174","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":[]}