{"doi":"10.1101/2021.04.26.441557","title":"The RNA m <sup>6</sup> A reader YTHDF2 controls NK cell anti-tumor and anti-viral immunity","abstract":"Abstract N 6 -methyladenosine (m 6 A) is the most prevalent post-transcriptional modification on RNA. NK cells are the predominant innate lymphoid cells that mediate anti-viral and anti-tumor immunity. However, whether and how m 6 A modifications affect NK cell immunity remains unknown. Here, we discover that YTHDF2, a well-known m 6 A reader, is upregulated in NK cells upon activation by cytokines, tumors, and cytomegalovirus infection. Ythdf2 deficiency in NK cells impairs NK cell anti-tumor and anti-viral activity in vivo . YTHDF2 maintains NK cell homeostasis and terminal maturation, correlating with modulating NK cell trafficking and regulating Eomes, respectively. YTHDF2 promotes NK cell effector function and is required for IL-15-mediated NK cell survival and proliferation by forming a STAT5-YTHDF2 positive feedback loop. Transcriptome-wide screening identifies Tardbp to be involved in cell proliferation or survival as a YTHDF2-binding target in NK cells. Collectively, we elucidate the biological roles of m 6 A modifications in NK cells and highlight a new direction to harness NK cell anti-tumor immunity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":218671,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9602,"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":623297,"name":"Jiazhuo Yan","orcid":"0000-0001-9233-7185","position":1,"is_corresponding":false},{"id":622924,"name":"Tasha Barr","orcid":"0000-0003-1404-7830","position":2,"is_corresponding":false},{"id":323591,"name":"Jianying Zhang","orcid":"0000-0003-2938-9526","position":3,"is_corresponding":false},{"id":78255,"name":"Zhenhua Chen","orcid":"0000-0002-1381-0235","position":4,"is_corresponding":false},{"id":336121,"name":"Li‐Shu Wang","orcid":"0000-0002-6500-6943","position":5,"is_corresponding":false},{"id":61584,"name":"Joseph C. Sun","orcid":"0000-0001-8062-9033","position":6,"is_corresponding":false},{"id":106277,"name":"Jianjun Chen","orcid":"0000-0003-3749-2902","position":7,"is_corresponding":false},{"id":3645,"name":"Michael A. Caligiuri","orcid":"0000-0002-4095-3020","position":8,"is_corresponding":false},{"id":253516,"name":"Jianhua Yu","orcid":"0000-0002-0326-3223","position":9,"is_corresponding":false},{"id":622923,"name":"Shoubao Ma","orcid":"0000-0002-7067-3599","position":0,"is_corresponding":true}],"reference_count":100,"raw_metadata":null,"created_at":"2026-07-18T23:53:29.626149Z","pmid":null,"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":[]}