{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:53:36Z","timestamp":1790967216844,"version":"4.1.0"},"reference-count":35,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"40","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32230018"],"award-info":[{"award-number":["32230018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32125007"],"award-info":[{"award-number":["32125007"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82341086"],"award-info":[{"award-number":["82341086"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32300521"],"award-info":[{"award-number":["32300521"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32422013"],"award-info":[{"award-number":["32422013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004147","name":"Tsinghua University","doi-asserted-by":"publisher","award":["TsienTang Life Science Development Fund"],"award-info":[{"award-number":["TsienTang Life Science Development Fund"]}],"id":[{"id":"10.13039\/501100004147","id-type":"DOI","asserted-by":"publisher"}]},{"name":"State Key Laboratory of Microbial Technology","award":["SKLMTIJP-2024-02"],"award-info":[{"award-number":["SKLMTIJP-2024-02"]}],"id":[{"id":"https:\/\/ror.org\/03x08qn04","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Science & Technology Fundamental Resources Investigation Program","award":["2025FY100300"],"award-info":[{"award-number":["2025FY100300"]}]},{"name":"Shenzhen Science and Technology Program","award":["AI2026009"],"award-info":[{"award-number":["AI2026009"]}]},{"name":"New Cornerstone Science Foundation","award":["XPLORER PRIZE"],"award-info":[{"award-number":["XPLORER PRIZE"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,10,2]]},"abstract":"<jats:p>RNA molecules are inherently dynamic, forming complex structural ensembles of alternative conformations that direct their cellular functions. Current methods for resolving RNA structural heterogeneity and dynamics have been developed for short-read sequencing\u2013based structure probing, limiting their sensitivity and resolution. Here, we introduce DeCoRE (deconvolving complex RNA structural ensembles), a computational method that leverages direct RNA sequencing to resolve RNA structural heterogeneity and dynamics at the individual transcript level. DeCoRE combines enhanced structural signal detection with direct clustering of sequencing reads to sensitively deconvolve RNA structural ensembles at single-nucleotide resolution. We demonstrate DeCoRE\u2019s capabilities by resolving the known alternative conformations of the lysine and TPP riboswitches and uncover a previously uncharacterized cotranscriptional folding pathway of bacterial ribosomal RNA, where two conformations coexist during early elongation and progressively converge into a single mature conformation. DeCoRE represents a powerful tool for dissecting RNA structural heterogeneity and dynamics, advancing our understanding of RNA function.<\/jats:p>","DOI":"10.1126\/sciadv.aef0670","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:59:16Z","timestamp":1790963956000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["DeCoRE: A computational method to resolve RNA structural heterogeneity from RNA structure probing data by direct RNA sequencing"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5993-1200","authenticated-orcid":true,"given":"Yong","family":"Huang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Membrane Biology, MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Beijing Advanced Innovation Center for Structural Biology &amp; Frontier Research Center for Biological Structure, Tsinghua-Peking Center for Life Sciences, Center for Life Sciences and Artificial intelligence, School of Life Sciences, Tsinghua University, Beijing 100084, China."},{"name":"State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1949-2979","authenticated-orcid":true,"given":"Jinsong","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Beijing Advanced Innovation Center for Structural Biology &amp; Frontier Research Center for Biological Structure, Tsinghua-Peking Center for Life Sciences, Center for Life Sciences and Artificial intelligence, School of Life Sciences, Tsinghua University, Beijing 100084, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1400-2157","authenticated-orcid":true,"given":"Lei","family":"Sun","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 266237, China."},{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4913-0338","authenticated-orcid":true,"given":"Qiangfeng Cliff","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Beijing Advanced Innovation Center for Structural Biology &amp; Frontier Research Center for Biological Structure, Tsinghua-Peking Center for Life Sciences, Center for Life Sciences and Artificial intelligence, School of Life Sciences, Tsinghua University, Beijing 100084, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00748-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0136-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2022.167665"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902271116"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio842"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.035"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2021.05.009"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-021-2116-2"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01623-y"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1407306111"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2253-5"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01075-w"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.02.009"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0712-z"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2022.100097"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-023-01862-7"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05135-9"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107317"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2021.1978215"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27393-3"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00285-007-0107-5"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13015-016-0070-z"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.4161\/rna.7.1.10489"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1128451"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25357-1"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa921"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","unstructured":"L. Sch\u00e4rfen I. W. Vock M. D. Simon K. M. Neugebauer Rapid folding of nascent RNA regulates eukaryotic RNA biogenesis. bioRxiv 2024.2011. 2026.625435 (2024); https:\/\/biorxiv.org\/content\/10.1101\/2024.11.26.625435v1.","DOI":"10.1101\/2024.11.26.625435"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx617"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.007"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","unstructured":"J. Mari\u0107 I. Sovi\u0107 K. Kri\u017eanovi\u0107 N. Nagarajan M. \u0160iki\u0107 Graphmap2-splice-aware RNA-seq mapper for long reads. bioRxiv 720458 (2019); https:\/\/biorxiv.org\/content\/10.1101\/720458v1.full.","DOI":"10.1101\/720458"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty191"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3444"},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","unstructured":"L. McInnes J. Healy J. Melville Umap: Uniform manifold approximation and projection for dimension reduction. arXiv:1802.03426 [stat.ML] (2018).","DOI":"10.21105\/joss.00861"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2019.09.020"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1727-y"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aef0670","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:59:29Z","timestamp":1790963969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aef0670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,2]]},"references-count":35,"journal-issue":{"issue":"40","published-print":{"date-parts":[[2026,10,2]]}},"alternative-id":["10.1126\/sciadv.aef0670"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aef0670","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,2]]},"assertion":[{"value":"2025-12-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaef0670"}}