{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T11:56:48Z","timestamp":1782129408721,"version":"3.54.5"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"content-version":"vor","delay-in-days":71,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-21-CE12-0028-01"],"award-info":[{"award-number":["ANR-21-CE12-0028-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["ALZ201912009641"],"award-info":[{"award-number":["ALZ201912009641"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003768","name":"University of Strasbourg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003768","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004100","name":"Labex","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004100","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015867","name":"DISTALZ","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015867","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tau protein plays a central role in Alzheimer\u2019s disease (AD) and other tauopathies. Tau proteins aggregate in degenerating neurons and their expression level is critical for disease development and progression. In addition, the generation of truncated Tau species is involved in the pathological process. In the human brain, several N-terminally truncated Tau species (including Met11- and Met127-Tau) have been detected. However, both the mechanisms of their synthesis and their relevance for the diseases remain largely unclear. Several Tau messenger RNA (mRNA) isoforms with distinct 5\u2032 untranslated regions\u00a0(5\u2032UTRs) were found in brains with tauopathies. In addition, single substitutions in the N-terminal coding sequence of Tau, namely R5H, R5L and R5C, have been associated with AD, progressive supranuclear palsy and Parkinson\u2019s disease, respectively. Here, we investigated how the 5\u2032 end of Tau mRNAs and the N-terminal mutations affect\u00a0Tau protein synthesis. We show that both the length of the 5\u2032UTR of Tau mRNAs and the N-terminal coding sequence largely modulate the expression level of Tau. Truncated Tau protein species are generated by an alternative translation initiation event. Thereafter, we show that the disease-associated mutations at codon #5 also increase the expression, mostly due to secondary structure modifications of the corresponding mRNAs.<\/jats:p>","DOI":"10.1093\/narmme\/ugae023","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T03:05:08Z","timestamp":1733886308000},"source":"Crossref","is-referenced-by-count":5,"title":["FTLD-MAPT mutations and short 5\u2032UTR Tau mRNAs increase Tau translation"],"prefix":"10.1093","volume":"1","author":[{"given":"Paulo\u00a0J","family":"da\u00a0Costa","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Strasbourg, Institut de Biologie Mol\u00e9culaire et Cellulaire, Architecture et R\u00e9activit\u00e9 de l\u2019ARN, CNRS UPR9002, 2, all\u00e9e Konrad Roentgen , F-67084\u00a0 Strasbourg ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Perret","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, Institut de Biologie Mol\u00e9culaire et Cellulaire, Architecture et R\u00e9activit\u00e9 de l\u2019ARN, CNRS UPR9002, 2, all\u00e9e Konrad Roentgen , F-67084\u00a0 Strasbourg ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Bu\u00e9e","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lille, INSERM, CHU-Lille, UMR-S1172, Alzheimer & Tauopathies\u2014LilNCog (Lille Neurosciences & Cognition) ,\u00a0Rue Michel Polonowski,\u00a0F-59000\u00a0 Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malika","family":"Hamdane","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lille, INSERM, CHU-Lille, UMR-S1172, Alzheimer & Tauopathies\u2014LilNCog (Lille Neurosciences & Cognition) ,\u00a0Rue Michel Polonowski,\u00a0F-59000\u00a0 Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9724-4025","authenticated-orcid":false,"given":"Franck","family":"Martin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, Institut de Biologie Mol\u00e9culaire et Cellulaire, Architecture et R\u00e9activit\u00e9 de l\u2019ARN, CNRS UPR9002, 2, all\u00e9e Konrad Roentgen , F-67084\u00a0 Strasbourg ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"2025010217143558600_B1","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.1091\/mbc.e14-06-1099","article-title":"Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons","volume":"25","author":"Janning","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"2025010217143558600_B2","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1126\/science.aat1780","article-title":"Near-atomic model of microtubule\u2013tau interactions","volume":"360","author":"Kellogg","year":"2018","journal-title":"Science"},{"key":"2025010217143558600_B3","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3389\/fnagi.2019.00204","article-title":"Role of tau as a microtubule-associated protein: structural and functional aspects","volume":"11","author":"Barbier","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"2025010217143558600_B4","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s40478-017-0489-6","article-title":"Atypical, non-standard functions of the microtubule associated Tau protein","volume":"5","author":"Sotiropoulos","year":"2017","journal-title":"Acta Neuropathol. Commun."},{"key":"2025010217143558600_B5","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1084\/jem.20161731","article-title":"Tau deletion promotes brain insulin resistance","volume":"214","author":"Marciniak","year":"2017","journal-title":"J. Exp. Med."},{"key":"2025010217143558600_B6","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.nbd.2015.09.003","article-title":"Prefibrillar Tau oligomers alter the nucleic acid protective function of Tau in hippocampal neurons in vivo","volume":"82","author":"Violet","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"2025010217143558600_B7","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1016\/j.neurobiolaging.2014.05.005","article-title":"Cognition and hippocampal synaptic plasticity in mice with a homozygous tau deletion","volume":"35","author":"Ahmed","year":"2014","journal-title":"Neurobiol. 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Biol."},{"key":"2025010217143558600_B10","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1002\/alz.12452","article-title":"Current directions in tau research: highlights from Tau 2020","volume":"18","author":"Sexton","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"2025010217143558600_B11","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3390\/biomedicines10020241","article-title":"Tau mRNA metabolism in neurodegenerative diseases: a tangle journey","volume":"10","author":"da\u00a0Costa","year":"2022","journal-title":"Biomedicines"},{"key":"2025010217143558600_B12","doi-asserted-by":"crossref","first-page":"9207","DOI":"10.3390\/ijms22179207","article-title":"Tau protein interaction partners and their roles in Alzheimer\u2019s disease and other tauopathies","volume":"22","author":"Sinsky","year":"2021","journal-title":"Int. J. Mol. 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Genet."},{"key":"2025010217143558600_B29","doi-asserted-by":"crossref","first-page":"3582","DOI":"10.1016\/j.febslet.2006.05.029","article-title":"Truncated tau from sporadic Alzheimer\u2019s disease suffices to drive neurofibrillary degeneration in vivo","volume":"580","author":"Zilka","year":"2006","journal-title":"FEBS Lett."},{"key":"2025010217143558600_B30","doi-asserted-by":"crossref","first-page":"10252","DOI":"10.1073\/pnas.0703676104","article-title":"Stepwise proteolysis liberates tau fragments that nucleate the Alzheimer-like aggregation of full-length tau in a neuronal cell model","volume":"104","author":"Wang","year":"2007","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2025010217143558600_B31","doi-asserted-by":"crossref","first-page":"9659","DOI":"10.1038\/srep09659","article-title":"Role of the Tau N-terminal region in microtubule stabilization revealed by new endogenous truncated forms","volume":"5","author":"Derisbourg","year":"2015","journal-title":"Sci. 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Sci."},{"key":"2025010217143558600_B56","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1126\/science.aba4904","article-title":"Structure of a human 48S translational initiation complex","volume":"369","author":"Brito\u00a0Querido","year":"2020","journal-title":"Science"},{"key":"2025010217143558600_B57","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1056\/NEJMra2215795","article-title":"Messenger RNA translation defects in neurodegenerative diseases","volume":"388","author":"Storkebaum","year":"2023","journal-title":"N. Engl. J. 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