{"created":"2023-05-15T16:49:28.795983+00:00","id":26952,"links":{},"metadata":{"_buckets":{"deposit":"7c87dac9-fbd4-453b-8b53-8692f71e57bc"},"_deposit":{"created_by":6,"id":"26952","owners":[6],"pid":{"revision_id":0,"type":"depid","value":"26952"},"status":"published"},"_oai":{"id":"oai:nagasaki-u.repo.nii.ac.jp:00026952","sets":["73:74"]},"author_link":["119987","119981","119988","119985","119984","119994","119990","119989","119983","119982","119992","119991","119993","119986"],"item_2_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2021-09-21","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"19","bibliographicPageEnd":"9651","bibliographicPageStart":"9623","bibliographicVolumeNumber":"11","bibliographic_titles":[{"bibliographic_title":"Theranostics"}]}]},"item_2_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Microglia are the primary cellular source of type I interferons (I-IFNs) in the brain upon neurotropic virus infection. Although the I-IFN-based antiviral innate immune response is crucial for eliminating viruses, overproduction led to immune disorders. Therefore, the relatively long-lasting I-IFNs must be precisely controlled, but the regulatory mechanism for the innate antiviral response in microglia remains largely unknown. Long non-coding RNAs (lncRNAs) are being recognized as crucial factors in numerous diseases, but their regulatory roles in the innate antiviral response in microglia are undefined.\nMethods: The high-throughput RNA sequencing was performed to obtain differentially expressed lncRNAs (DELs) in primary microglia infected with or without the neurotropic herpes simplex virus type 1 (HSV-1). We selected four DELs ranked in the top 15 in basic level and their fold change induced by HSV-1, i.e., FPKMHSV-1/FPKMCells.We subsequently found a key lncRNA affecting the innate antiviral response of microglia significantly. We next used dual-luciferase reporter assays, bioinformatical tools, and truncation mutants of both lncRNA and targeted proteins to elucidate the downstream and upstream mechanism of action of lncRNA. Further, we established microglia-specific knock-in (KI) mice to investigate the role of lncRNA in vivo.\nResults: We identified a long intergenic non-coding RNA, linc-AhRA, involved in regulating the innate antiviral response in murine microglia. linc-AhRA is activated by aryl hydrocarbon receptor (AhR) and restricts I-IFN production in microglia upon neurotropic herpesvirus infection and innate immune stimulation. Mechanistically, linc-AhRA binds to both tripartite motif-containing 27 (TRIM27) and TANK-binding kinase 1 (TBK1) through its conserved 117nt fragment as a molecular scaffold to enhance TRIM27-TBK1 interaction. This interaction facilitates the TRIM27-mediated ubiquitination of TBK1 and results in ubiquitin-proteasome-dependent degradation of TBK1. Consequently, linc-AhRA suppresses I-IFN production through facilitating TBK1 degradation and limits the microglial innate immune response against neurotropic herpesvirus infection. Microglia-specific KI of linc-AhRA mice shows a weakened antiviral immune response upon neurotropic herpesvirus challenge due to a reduction of TBK1 in microglia.\nConclusion: Our findings indicate that linc-AhRA is a negative regulator of I-IFN production in microglia to avoid excessive autoimmune responses. These findings uncover a previously unappreciated role for lncRNA conserved fragments in the innate antiviral response, providing a strong foundation for developing nucleotide drugs based on conserved functional fragments within lncRNAs.","subitem_description_type":"Abstract"}]},"item_2_description_63":{"attribute_name":"引用","attribute_value_mlt":[{"subitem_description":"Theranostics, 11(19), pp. 9623-9651; 2021","subitem_description_type":"Other"}]},"item_2_publisher_33":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Ivyspring International Publisher"}]},"item_2_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.7150/thno.64880","subitem_relation_type_select":"DOI"}}]},"item_2_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions."}]},"item_2_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1838-7640","subitem_source_identifier_type":"ISSN"}]},"item_2_version_type_16":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Wang, Yiliang"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Luo, Weisheng"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Huang, Lianzhou"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Xiao, Ji"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Song, Xiaowei"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Li, Feng"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Ma, Yuying"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Wang, Xiaohui"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Jin, Fujun"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Liu, Ping"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Zhu, Yexuan"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Kitazato, Kaio"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Wang, Yifei"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Ren, Zhe"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-12-21"}],"displaytype":"detail","filename":"Theranostics11_9623.pdf","filesize":[{"value":"4.6 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Theranostics11_9623.pdf","url":"https://nagasaki-u.repo.nii.ac.jp/record/26952/files/Theranostics11_9623.pdf"},"version_id":"27823b07-13d5-4ad4-a02c-2c81f81b2eef"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Microglia","subitem_subject_scheme":"Other"},{"subitem_subject":"neurotropic virus","subitem_subject_scheme":"Other"},{"subitem_subject":"long non-coding RNA","subitem_subject_scheme":"Other"},{"subitem_subject":"conserved fragment","subitem_subject_scheme":"Other"},{"subitem_subject":"TBK1","subitem_subject_scheme":"Other"},{"subitem_subject":"TRIM27","subitem_subject_scheme":"Other"},{"subitem_subject":"aryl hydrocarbon receptor (AhR)","subitem_subject_scheme":"Other"}]},"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":"A novel lncRNA linc-AhRA negatively regulates innate antiviral response in murine microglia upon neurotropic herpesvirus infection","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"A novel lncRNA linc-AhRA negatively regulates innate antiviral response in murine microglia upon neurotropic herpesvirus infection"}]},"item_type_id":"2","owner":"6","path":["74"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-12-21"},"publish_date":"2021-12-21","publish_status":"0","recid":"26952","relation_version_is_last":true,"title":["A novel lncRNA linc-AhRA negatively regulates innate antiviral response in murine microglia upon neurotropic herpesvirus infection"],"weko_creator_id":"6","weko_shared_id":-1},"updated":"2023-05-15T20:05:01.581215+00:00"}