{"doi":"10.1021/acsnano.4c04625","title":"Unraveling RNA Conformation Dynamics in Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episode Syndrome with Solid-State Nanopores","abstract":"This study investigates transfer ribonucleic acid (tRNA) conformational dynamics in the context of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) using solid-state silicon nitride (SiN) nanopore technology. SiN nanopores in thin membranes with specific dimensions exhibit high signal resolution, enabling real-time and single-molecule electronic detection of tRNA conformational changes. We focus on human mitochondrial tRNALeu(UAA) (mt-Leu(UAA)) that decodes Leu codons UUA/UUG (UUR) during protein synthesis on the mt-ribosome. The single A14G substitution in mt-Leu(UAA) is the major cause of MELAS disease. Measurements of current blockades and dwell times reveal distinct conformational dynamics of the wild-type (WT) and the A14G variant of mt-Leu(UAA) in response to the conserved post-transcriptional m 1 G9 methylation. While the m 1 G9-modified WT transcript adopts a more stable structure relative to the unmodified transcript, the m 1 G9-modified MELAS transcript adopts a less stable structure relative to the unmodified transcript. Notably, these differential features were observed at 0.4 M KCl, but not at 3 M KCl, highlighting the importance of experimental settings that are closer to physiological conditions. This work demonstrates the feasibility of the nanopore platform to discern tRNA molecules that differ by a single-nucleotide substitution or by a single methylation event, providing an important step forward to explore changes in the conformational dynamics of other RNA molecules in human diseases.","journal":"ACS Nano","year":2024,"id":430429,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9646,"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":1233430,"name":"Kyril Kavetsky","orcid":"0000-0001-7213-1219","position":1,"is_corresponding":false},{"id":1233431,"name":"Chih‐Yuan Lin","orcid":"0000-0002-2425-5548","position":2,"is_corresponding":false},{"id":451352,"name":"Sunita Maharjan","orcid":"0000-0002-7099-1802","position":3,"is_corresponding":false},{"id":488621,"name":"Howard Gamper","orcid":"0000-0001-9007-8546","position":4,"is_corresponding":false},{"id":345743,"name":"Nan‐Sheng Li","orcid":"0000-0002-1185-3688","position":5,"is_corresponding":false},{"id":345746,"name":"Joseph A. Piccirilli","orcid":"0000-0002-0541-6270","position":6,"is_corresponding":false},{"id":17829,"name":"Ya-Ming Hou","orcid":"0000-0001-6546-2597","position":7,"is_corresponding":false},{"id":350206,"name":"Marija Drndić","orcid":"0000-0002-8104-2231","position":8,"is_corresponding":false},{"id":1233429,"name":"Srilahari Namani","orcid":"0000-0003-3146-8880","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T01:59:16.092672Z","pmid":"38906834","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":[]}