{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:29:47Z","timestamp":1792042187878,"version":"4.4.0"},"reference-count":80,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"30","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,7,25]]},"abstract":"<jats:p>\n                    Mutations in the\n                    <jats:italic>FUS<\/jats:italic>\n                    gene cause aggressive amyotrophic lateral sclerosis (ALS-FUS). Beyond mRNA,\n                    <jats:italic>FUS<\/jats:italic>\n                    generates partially processed transcripts retaining introns 6 and 7. We demonstrate that these FUSint6&amp;7-RNA molecules form nuclear condensates, scaffolded by the highly structured intron 7 and associated with nuclear speckles. Using hybridization-proximity labeling proteomics, we show that the FUSint6&amp;7-RNA condensates are enriched for splicing factors and the N6-methyladenosine (m6A) reader YTHDC1. These ribonucleoprotein structures facilitate posttranscriptional FUS splicing and depend on m6A\/YTHDC1 for integrity. In cells expressing mutant FUS, FUSint6&amp;7-RNAs become hypermethylated, which in turn stimulates their condensation and splicing. We further show that FUS protein is repelled by m6A. Thus, ALS-FUS mutations may cause abnormal activation of FUS posttranscriptional splicing through altered RNA methylation. Notably, ectopic expression of FUS intron 7 sequences dissolves endogenous FUSint6&amp;7-RNA condensates, down-regulating FUS mRNA and protein. Our findings reveal a condensation-dependent mechanism regulating FUS splicing, with possible therapeutic implications for ALS.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adx1357","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T17:58:39Z","timestamp":1753293519000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["M6A-dependent RNA condensation underlies FUS autoregulation and can be harnessed for ALS therapy development"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1656-5508","authenticated-orcid":true,"given":"Wan-Ping","family":"Huang","sequence":"first","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) and Neuroscience Institute, University of Sheffield, Sheffield, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7310-9769","authenticated-orcid":true,"given":"Vedanth","family":"Kumar","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) and Neuroscience Institute, University of Sheffield, Sheffield, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Yap","sequence":"additional","affiliation":[{"name":"Centre for Developmental Biology, King\u2019s College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2545-3757","authenticated-orcid":true,"given":"Haiyan","family":"An","sequence":"additional","affiliation":[{"name":"Medical School, Swansea University, Swansea, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7628-1484","authenticated-orcid":true,"given":"Sabin J.","family":"John","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) and Neuroscience Institute, University of Sheffield, Sheffield, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5427-2560","authenticated-orcid":true,"given":"Rachel E.","family":"Hodgson","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) and Neuroscience Institute, University of Sheffield, Sheffield, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Sanchez","family":"Avila","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) and Neuroscience Institute, University of Sheffield, Sheffield, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3030-084X","authenticated-orcid":true,"given":"Emily","family":"Day","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN) and Neuroscience Institute, University of Sheffield, Sheffield, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany C. 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