{"doi":"10.1101/2020.11.12.377127","title":"Caspases switch off m <sup>6</sup> A RNA modification pathway to reactivate a ubiquitous human tumor virus","abstract":"Abstract The methylation of RNA at the N6 position of adenosine (m 6 A) orchestrates multiple biological processes to control development, differentiation, and cell cycle, as well as various aspects of the virus life cycle. How the m 6 A RNA modification pathway is regulated to finely tune these processes remains poorly understood. Here, we discovered the m 6 A reader YTHDF2 as a caspase substrate via proteome-wide prediction, followed by in vitro and in vivo validations. We further demonstrated that cleavage-resistant YTHDF2 blocks, while cleavage-mimicking YTHDF2 fragments promote, the replication of a common human oncogenic virus, Epstein-Barr virus (EBV). Intriguingly, our study revealed a feedback regulation between YTHDF2 and caspase-8 via m 6 A modification of CASP8 mRNA and YTHDF2 cleavage during EBV replication. Further, we discovered that caspases cleave multiple components within the m 6 A RNA modification pathway to benefit EBV replication. Together, our study establishes that caspase disarming of the m 6 A RNA modification machinery fosters EBV reactivation. Teaser Cellular m 6 A RNA modification machinery is cleaved by caspases to foster the reproduction of a common human tumor virus","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":131681,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":585819,"name":"Yucheng Zhang","orcid":"0000-0002-7844-3202","position":1,"is_corresponding":false},{"id":585820,"name":"Yunash Maharjan","orcid":"0000-0003-0453-9778","position":2,"is_corresponding":false},{"id":585821,"name":"Febri Gunawan Sugiokto","orcid":"0009-0004-2097-2744","position":3,"is_corresponding":false},{"id":300846,"name":"Jun Wan","orcid":"0000-0001-9286-6562","position":4,"is_corresponding":false},{"id":585822,"name":"Renfeng Li","orcid":"0000-0002-9226-4470","position":5,"is_corresponding":false},{"id":585818,"name":"Kun Zhang","orcid":"0000-0001-5696-2426","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-18T23:16:03.875886Z","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":[]}