{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:03:26Z","timestamp":1791489806608,"version":"4.3.4"},"reference-count":95,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"34","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,8,22]]},"abstract":"<jats:p>\n            Splicing factor proline- and glutamine-rich (SFPQ) is an RNA binding protein that broadly regulates RNA metabolism. Although its nuclear roles are well studied, evidence of SFPQ\u2019s cytoplasmic functionality is emerging. Altered expression and nuclear-to-cytoplasmic redistribution of SFPQ have been recognized in amyotrophic lateral sclerosis (ALS) pathology, yet the mechanistic bases for these phenomena remain undetermined. We identified altered\n            <jats:italic toggle=\"yes\">SFPQ<\/jats:italic>\n            splicing in ALS, increasing the expression of an alternative mRNA isoform lacking a nuclear localization sequence, which we termed \u201c\n            <jats:italic toggle=\"yes\">altSFPQ<\/jats:italic>\n            .\u201d We find that\n            <jats:italic toggle=\"yes\">altSFPQ<\/jats:italic>\n            mRNA contributes to SFPQ autoregulation and is highly unstable yet exhibits context-specific translation with cytoplasm-predominant localization. Notably, reduced canonical\n            <jats:italic toggle=\"yes\">SFPQ<\/jats:italic>\n            coincides with increased\n            <jats:italic toggle=\"yes\">altSFPQ<\/jats:italic>\n            transcript expression in familial and sporadic ALS models, providing a mechanistic basis for SFPQ nuclear-to-cytoplasmic redistribution in patients with ALS. Last, we observe that the altSFPQ protein has reduced phase separation potential and differential protein binding compared to its canonical counterpart, providing insight into its mechanistic relevance to physiology and ALS pathogenesis.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adt4814","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T17:58:56Z","timestamp":1755885536000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["An alternative cytoplasmic SFPQ isoform with reduced phase separation potential is up-regulated in ALS"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7051-4961","authenticated-orcid":true,"given":"Jacob","family":"Neeves","sequence":"first","affiliation":[{"name":"Department of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK."},{"name":"The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8588-9870","authenticated-orcid":true,"given":"Marija","family":"Petri\u0107 Howe","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK."},{"name":"The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1504-7245","authenticated-orcid":true,"given":"Oliver J.","family":"Ziff","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK."},{"name":"The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0517-7142","authenticated-orcid":true,"given":"Beth","family":"Callaghan","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8381-7830","authenticated-orcid":true,"given":"Daniel","family":"Jutzi","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at King\u2019s College London, London, UK."},{"name":"Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology &amp; Neuroscience, King\u2019s College London, 125 Coldharbour Lane, London SE5 9NU, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6891-1148","authenticated-orcid":true,"given":"Koustav","family":"Pal","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK."},{"name":"The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoros I.","family":"Roumeliotis","sequence":"additional","affiliation":[{"name":"Functional Proteomics team, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0881-5477","authenticated-orcid":true,"given":"Jyoti","family":"Choudhary","sequence":"additional","affiliation":[{"name":"Functional Proteomics team, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6820-5534","authenticated-orcid":true,"given":"Adrian M.","family":"Isaacs","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at University College London, London, UK."},{"name":"Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Rigo","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals, Carlsbad, CA 92010, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9887-6251","authenticated-orcid":true,"given":"C. 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