{"created":"2023-06-26T11:01:26.361662+00:00","id":2142,"links":{},"metadata":{"_buckets":{"deposit":"fc14cc0c-b91b-40a5-81e0-b58aab558e2a"},"_deposit":{"created_by":30,"id":"2142","owners":[30],"pid":{"revision_id":0,"type":"depid","value":"2142"},"status":"published"},"_oai":{"id":"oai:oist.repo.nii.ac.jp:00002142","sets":["6:40"]},"author_link":["14107","14102","14103","14110","14108","14104","14109","14106","14105","14111"],"item_10001_biblio_info_7":{"attribute_name":"Bibliographic Information","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2021-03-04","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"6","bibliographicPageEnd":"3184","bibliographicPageStart":"3168","bibliographicVolumeNumber":"49","bibliographic_titles":[{},{"bibliographic_title":"Nucleic Acids Research","bibliographic_titleLang":"en"}]}]},"item_10001_creator_3":{"attribute_name":"Author","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Ziff, Oliver J"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Taha, Doaa M"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Crerar, Hamish"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Clarke, Benjamin E"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Chakrabarti, Anob M"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Kelly, Gavin"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Neeves, Jacob"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Tyzack, Giulia E"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Luscombe, Nicholas M"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Patani, Rickie"}],"nameIdentifiers":[{}]}]},"item_10001_description_5":{"attribute_name":"Abstract","attribute_value_mlt":[{"subitem_description":"Reactive astrocytes are implicated in amyotrophic lateral sclerosis (ALS), although the mechanisms controlling reactive transformation are unknown. We show that decreased intron retention (IR) is common to human-induced pluripotent stem cell (hiPSC)-derived astrocytes carrying ALS-causing mutations in VCP, SOD1 and C9orf72. Notably, transcripts with decreased IR and increased expression are overrepresented in reactivity processes including cell adhesion, stress response and immune activation. This was recapitulated in public-datasets for (i) hiPSC-derived astrocytes stimulated with cytokines to undergo reactive transformation and (ii) in vivo astrocytes following selective deletion of TDP-43. We also re-examined public translatome sequencing (TRAP-seq) of astrocytes from a SOD1 mouse model, which revealed that transcripts upregulated in translation significantly overlap with transcripts exhibiting decreased IR. Using nucleocytoplasmic fractionation of VCP mutant astrocytes coupled with mRNA sequencing and proteomics, we identify that decreased IR in nuclear transcripts is associated with enhanced nonsense mediated decay and increased cytoplasmic expression of transcripts and proteins regulating reactive transformation. These findings are consistent with a molecular model for reactive transformation in astrocytes whereby poised nuclear reactivity-related IR transcripts are spliced, undergo nuclear-to-cytoplasmic translocation and translation. Our study therefore provides new insights into the molecular regulation of reactive transformation in astrocytes.","subitem_description_type":"Other"}]},"item_10001_publisher_8":{"attribute_name":"Publisher","attribute_value_mlt":[{"subitem_publisher":"Oxford University Press on behalf of Nucleic Acids Research."}]},"item_10001_relation_13":{"attribute_name":"PubMedNo.","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"info:pmid/33684213","subitem_relation_type_select":"PMID"}}]},"item_10001_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"info:doi/10.1093/nar/gkab115","subitem_relation_type_select":"DOI"}}]},"item_10001_relation_17":{"attribute_name":"Related site","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://academic.oup.com/nar/article/49/6/3168/6155937","subitem_relation_type_select":"URI"}}]},"item_10001_rights_15":{"attribute_name":"Rights","attribute_value_mlt":[{"subitem_rights":"© 2021 The Author(s)."}]},"item_10001_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0305-1048","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"1362-4962","subitem_source_identifier_type":"ISSN"}]},"item_10001_version_type_20":{"attribute_name":"Author's flag","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-05-28"}],"displaytype":"detail","filename":"Ziff-2021-Reactive astrocytes in ALS display d.pdf","filesize":[{"value":"6.4 MB"}],"format":"application/pdf","license_note":"Creative Commons Attribution 4.0 International(https://creativecommons.org/licenses/by/4.0/)","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Ziff-2021-Reactive astrocytes in ALS display d","url":"https://oist.repo.nii.ac.jp/record/2142/files/Ziff-2021-Reactive astrocytes in ALS display d.pdf"},"version_id":"c15be17b-1ed9-49fd-afe3-a6dd44fdff0b"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Reactive astrocytes in ALS display diminished intron retention","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Reactive astrocytes in ALS display diminished intron retention","subitem_title_language":"en"}]},"item_type_id":"10001","owner":"30","path":["40"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-05-28"},"publish_date":"2021-05-28","publish_status":"0","recid":"2142","relation_version_is_last":true,"title":["Reactive astrocytes in ALS display diminished intron retention"],"weko_creator_id":"30","weko_shared_id":30},"updated":"2023-06-26T11:36:28.385323+00:00"}