{"created":"2023-06-26T11:00:45.555062+00:00","id":1340,"links":{},"metadata":{"_buckets":{"deposit":"62db9fd6-c6eb-4a72-af35-8a6d6db3569d"},"_deposit":{"created_by":22,"id":"1340","owners":[22],"pid":{"revision_id":0,"type":"depid","value":"1340"},"status":"published"},"_oai":{"id":"oai:oist.repo.nii.ac.jp:00001340","sets":["7:200"]},"author_link":[],"item_10006_creator_3":{"attribute_name":"Author","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Mostafa, Dina","creatorNameLang":"en"}]}]},"item_10006_date_granted_11":{"attribute_name":"Degree Conferral Date","attribute_value_mlt":[{"subitem_dategranted":"2020-02-29"}]},"item_10006_degree_grantor_9":{"attribute_name":"Degree Conferrral Institution","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"Okinawa Institute of Science and Technology Graduate University"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"38005","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_10006_degree_name_8":{"attribute_name":"Degree","attribute_value_mlt":[{"subitem_degreename":"Doctor of Philosophy"}]},"item_10006_description_7":{"attribute_name":"Abstract","attribute_value_mlt":[{"subitem_description":"Functional analysis of CCR4-NOT complex in pancreatic β cell\nPancreatic β cells are responsible for production and secretion of insulin in response to increasing blood glucose levels. Therefore, defects in pancreatic β cell function lead to hyperglycemia and diabetes mellitus. While extensive research has focused on signaling, transcriptional, and epigenetic regulation in β cells, how post-transcriptional mechanisms influence the β cell gene expression program is largely unknown. The carbon catabolite repression 4 (CCR4)–negative on TATA-less (NOT) complex (CCR4-NOT complex), a major deadenylase conserved in eukaryotes, catalyzes mRNA deadenylation which is the rate limiting step in mRNA decay pathway. The CCR4-NOT complex has been implicated in the development of metabolic diseases. However, whether the CCR4-NOT complex affects β cell function is not addressed. In this thesis, I aim to understand the importance of post-transcriptional regulation in β cells by generating mice lacking the Cnot3 gene, which encodes an essential CCR4-NOT complex subunit, in β cells. Suppression of CNOT3 in β cells caused β cell dysfunction and diabetes. This was associated with the decreased expression of β cell-specific genes and increased expression of genes specifically repressed in β cells, called “β cell disallowed genes”. By combining whole transcriptome and proteome analyses and subsequent validations using quantitative PCR (qPCR) and immunoblot analyses, I found that mRNA and protein expression patterns were largely different from normal β cells upon CNOT3 suppression, which was clearly relevant to the observed phenotypes. I also found that some β cell disallowed genes were stabilized in the absence of CNOT3, suggesting that their expression was maintained at low levels under the control of the CCR4-NOT complex. Together, this study uncovered mRNA deadenylation by CCR4-NOT complex as a novel molecular mechanism by which β cell identity and function are regulated.","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_10006_dissertation_number_12":{"attribute_name":"Degree Referral Number","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第43号"}]},"item_10006_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.15102/1394.00001210","subitem_identifier_reg_type":"JaLC"}]},"item_10006_rights_13":{"attribute_name":"Copyright Information","attribute_value_mlt":[{"subitem_rights":"© 2020 The Author. "}]},"item_10006_text_24":{"attribute_name":"Exam Date","attribute_value_mlt":[{"subitem_text_value":"2020-01-23"}]},"item_10006_version_type_18":{"attribute_name":"Version Format","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-04-02"}],"displaytype":"detail","filename":"Full Text.pdf","filesize":[{"value":"4.0 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Full Text","objectType":"fulltext","url":"https://oist.repo.nii.ac.jp/record/1340/files/Full Text.pdf"},"version_id":"e8b45be6-8110-4aa4-9c52-8bd9d383f36c"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-04-15"}],"displaytype":"detail","filename":"Final Exam Abstract.pdf","filesize":[{"value":"97.8 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Final Exam Abstract","objectType":"abstract","url":"https://oist.repo.nii.ac.jp/record/1340/files/Final Exam Abstract.pdf"},"version_id":"539171b6-085b-4ec4-8ac4-e5b7a124e5bf"}]},"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":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"CCR4-NOT複合体の膵臓β細胞における機能解析","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"CCR4-NOT複合体の膵臓β細胞における機能解析","subitem_title_language":"ja"},{"subitem_title":"Functional Analysis of CCR4-NOT Complex in Pancreatic β Cell","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"22","path":["200"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2020-04-02"},"publish_date":"2020-04-02","publish_status":"0","recid":"1340","relation_version_is_last":true,"title":["CCR4-NOT複合体の膵臓β細胞における機能解析"],"weko_creator_id":"22","weko_shared_id":-1},"updated":"2023-08-31T02:52:16.167573+00:00"}