{"data":{"id":"10.6084/m9.figshare.1291145.v2","type":"dois","attributes":{"doi":"10.6084/m9.figshare.1291145.v2","prefix":"10.6084","suffix":"m9.figshare.1291145.v2","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Costessi, Luisa","nameType":"Personal","givenName":"Luisa","familyName":"Costessi","affiliation":[],"nameIdentifiers":[]},{"name":"Porro, Fabiola","nameType":"Personal","givenName":"Fabiola","familyName":"Porro","affiliation":[],"nameIdentifiers":[]},{"name":"Iaconcig, Alessandra","nameType":"Personal","givenName":"Alessandra","familyName":"Iaconcig","affiliation":[],"nameIdentifiers":[]},{"name":"Muro, Andrés F","nameType":"Personal","givenName":"Andrés F","familyName":"Muro","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"TDP-43 regulates \u003ci\u003eβ-adducin\u003c/i\u003e (\u003ci\u003eAdd2\u003c/i\u003e) transcript stability"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"111714 Mental Health","subjectScheme":"FOR"},{"subject":"FOS: Health sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Health sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Computational Biology"},{"subject":"110309 Infectious Diseases","subjectScheme":"FOR"},{"subject":"Hematology"},{"subject":"Biological Sciences"},{"subject":"Neuroscience"},{"subject":"Molecular Biology"},{"subject":"Genetics"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Biological sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Cell Biology"},{"subject":"Biochemistry"}],"contributors":[],"dates":[{"date":"2015-10-15","dateType":"Created"},{"date":"2016-01-19","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1080/15476286.2014.996081","relatedIdentifierType":"DOI"},{"relationType":"IsPreviousVersionOf","relatedIdentifier":"10.6084/m9.figshare.1291145","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["3134002 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"TDP-43 is an RNA-binding protein involved in several steps of mRNA metabolism including transcription, splicing and stability. It is also involved in ALS and FTD, neurodegenerative diseases characterized by TDP-43 nuclear depletion. We previously identified TDP-43 as a binder of the downstream element (DSE) of the \u003ci\u003eβ-Adducin\u003c/i\u003e (\u003ci\u003eAdd2\u003c/i\u003e) brain-specific polyadenylation site (A4 PAS), suggesting its involvement in pre-mRNA 3′ end processing. Here, by using chimeric minigenes, we showed that TDP-43 depletion in HeLa and HEK293 cells resulted in down-regulation of both the chimeric and endogenous \u003ci\u003eAdd2\u003c/i\u003e transcripts. Despite having confirmed TDP-43-DSE in vitro interaction, we demonstrated that the in vivo effect was not mediated by the TDP-43-DSE interaction. In fact, substitution of the \u003ci\u003eAdd2\u003c/i\u003e DSE with viral \u003ci\u003eE-SV40\u003c/i\u003e and \u003ci\u003eL-SV40\u003c/i\u003e DSEs, which are not TDP-43 targets, still resulted in decreased \u003ci\u003eAdd2\u003c/i\u003e mRNA levels after TDP-43 downregulation. In addition, we failed to show interaction between TDP-43 and key polyadenylation factors, such as CstF-64 and CPSF160 and excluded TDP-43 involvement in pre-mRNA cleavage and regulation of polyA tail length. These evidences allowed us to exclude the pre-hypothesized role of TDP43 in modulating 3′ end processing of \u003ci\u003eAdd2\u003c/i\u003e pre-mRNA. Finally, we showed that TDP-43 regulates \u003ci\u003eAdd2\u003c/i\u003e gene expression levels by increasing \u003ci\u003eAdd2\u003c/i\u003e mRNA stability. Considering that \u003ci\u003eAdd2\u003c/i\u003e in brain participates in synapse assembly, synaptic plasticity and their stability, and its genetic inactivation in mice leads to LTP, LTD, learning and motor-coordination deficits, we hypothesize that a possible loss of Add2 function by TDP-43 depletion may contribute to ALS and FTD disease states.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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