{"doi":"10.1101/2022.01.08.475504","title":"RNA binding to human METTL3-METTL14 restricts <i> N <sup>6</sup> </i> -deoxyadenosine methylation of DNA <i>in vitro</i>","abstract":"Abstract Methyltransferase like-3 (METTL3) and METTL14 complex transfers a methyl group from S -adenosyl-L-methionine to N 6 amino group of adenosine bases in RNA (m 6 A) and DNA (m 6 dA). Emerging evidence highlights a role of METTL3-METTL14 in the chromatin context, especially in processes where DNA and RNA are held in close proximity. However, a mechanistic framework about specificity for substrate RNA/DNA and their interrelationship remain unclear. By systematically studying methylation activity and binding affinity to a number of DNA and RNA oligos with different propensities to form inter- or intra-molecular duplexes or single-stranded molecules in vitro , we uncover an inverse relationship for substrate binding and methylation and show that METTL3-METTL14 preferentially catalyzes the formation of m 6 dA in single-stranded DNA (ssDNA), despite weaker binding affinity to DNA. In contrast, it binds structured RNAs with high affinity, but methylates the target adenosine in RNA (m 6 A) much less efficiently than it does in ssDNA. We also show that METTL3-METTL14-mediated methylation of DNA is largely regulated by structured RNA elements prevalent in long noncoding and other cellular RNAs.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":305574,"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":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":999426,"name":"Javier Mota","orcid":"0009-0002-6150-0714","position":1,"is_corresponding":false},{"id":240053,"name":"Siu‐Hong Chan","orcid":"0000-0002-9554-7273","position":2,"is_corresponding":false},{"id":892232,"name":"Johanna Villarreal","orcid":null,"position":3,"is_corresponding":false},{"id":240055,"name":"Nan Dai","orcid":"0000-0003-3268-1835","position":4,"is_corresponding":false},{"id":240052,"name":"Shailee Arya","orcid":"0000-0002-7689-7411","position":5,"is_corresponding":false},{"id":240060,"name":"Robert Hromas","orcid":"0000-0002-1916-6276","position":6,"is_corresponding":false},{"id":640937,"name":"Manjeet K. Rao","orcid":"0000-0001-7573-2677","position":7,"is_corresponding":false},{"id":121504,"name":"Ivan R Corrêa","orcid":"0000-0002-3169-6878","position":8,"is_corresponding":false},{"id":240061,"name":"Yogesh K. Gupta","orcid":"0000-0001-6372-5007","position":9,"is_corresponding":false},{"id":240054,"name":"Shan Qi","orcid":"0000-0003-0175-6267","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T00:32:41.290883Z","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":[]}