{"doi":"10.1093/bioadv/vbab046","title":"<i>N</i> 6-methyladenosine enhances post-transcriptional gene regulation by microRNAs","abstract":"Abstract Motivation N 6-methyladenosine (m6A) is the most prevalent modification in eukaryotic messenger RNAs. MicroRNAs (miRNAs) are abundant post-transcriptional regulators of gene expression. Correlation between m6A and miRNA-targeting sites has been reported to suggest possible involvement of m6A in miRNA-mediated gene regulation. However, it is unknown what the regulatory effects might be. In this study, we performed comprehensive analyses of high-throughput data on m6A and miRNA target binding and regulation. Results We found that the level of miRNA-mediated target suppression is significantly enhanced when m6A is present on target mRNAs. The evolutionary conservation for miRNA-binding sites with m6A modification is significantly higher than that for miRNA-binding sites without modification. These findings suggest functional significance of m6A modification in post-transcriptional gene regulation by miRNAs. We also found that methylated targets have more stable structure than non-methylated targets, as indicated by significantly higher GC content. Furthermore, miRNA-binding sites that can be potentially methylated are significantly less accessible without methylation than those that do not possess potential methylation sites. Since either RNA-binding proteins or m6A modification by itself can destabilize RNA structure, we propose a model in which m6A alters local target secondary structure to increase accessibility for efficient binding by Argonaute proteins, leading to enhanced miRNA-mediated regulation. Availability and implementation N/A.","journal":"Bioinformatics Advances","year":2022,"id":283042,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"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":959907,"name":"William Rennie","orcid":null,"position":1,"is_corresponding":false},{"id":959908,"name":"C. Steven Carmack","orcid":null,"position":2,"is_corresponding":false},{"id":478762,"name":"Jun Lü","orcid":"0000-0003-2726-7613","position":3,"is_corresponding":false},{"id":720347,"name":"Ye Ding","orcid":"0000-0003-3460-1122","position":4,"is_corresponding":false},{"id":959470,"name":"Shaveta Kanoria","orcid":"0000-0003-4609-1350","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T00:29:23.777809Z","pmid":"35098135","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":[]}