{"corpus_id":18182359,"paper_sha":"93adf8ba374993a2a77719089cb6750ca51a96e1","doi":"10.1093/nar/gkw1304","arxiv_id":null,"pmid":28053121,"pmcid":"5397167","mag_id":2569356794,"dblp_id":null,"acl_id":null,"title":"ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins","year":2017,"publication_date":"2017-01-04","venue":"Nucleic Acids Research","journal":{"name":"Nucleic Acids Research","pages":"4189 - 4201","volume":"45"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Intramural","Research Support, N.I.H., Extramural"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":66,"citation_count":47,"influential_citation_count":4,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"3' Untranslated Regions","mj":false,"ui":"D020413"},{"d":"Adenosine Deaminase","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D000243"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Cationic Amino Acid Transporter 2","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D027202"},{"d":"ELAV-Like Protein 1","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D000067780"},{"d":"Exoribonucleases","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D005095"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"RNA Editing","mj":false,"ui":"D017393"},{"d":"RNA Stability","mj":true,"ui":"D020871"},{"d":"RNA, Long Noncoding","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D062085"},{"d":"RNA-Binding Proteins","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D016601"}],"chemicals":[{"n":"3' Untranslated Regions","ui":"D020413","reg":"0"},{"n":"Adenosine Deaminase","ui":"D000243","reg":"EC 3.5.4.4"},{"n":"Cationic Amino Acid Transporter 2","ui":"D027202","reg":"0"},{"n":"ELAV-Like Protein 1","ui":"D000067780","reg":"0"},{"n":"Exoribonucleases","ui":"D005095","reg":"EC 3.1.-"},{"n":"RNA, Long Noncoding","ui":"D062085","reg":"0"},{"n":"RNA-Binding Proteins","ui":"D016601","reg":"0"},{"n":"Elavl1 protein, mouse","ui":"C000593997","reg":"0"},{"n":"ADAR2 protein, mouse","ui":"C000595151","reg":"EC 3.5.4.4"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Abstract Adenosine deaminases acting on RNA (ADARs) catalyze the editing of adenosine residues to inosine (A-to-I) within RNA sequences, mostly in the introns and UTRs (un-translated regions). The significance of editing within non-coding regions of RNA is poorly understood. Here, we demonstrate that association of ADAR2 with RNA stabilizes a subset of transcripts. ADAR2 interacts with and edits the 3΄UTR of nuclear-retained Cat2 transcribed nuclear RNA (Ctn RNA). In absence of ADAR2, the abundance and half-life of Ctn RNA are significantly reduced. Furthermore, ADAR2-mediated stabilization of Ctn RNA occurred in an editing-independent manner. Unedited Ctn RNA shows enhanced interaction with the RNA-binding proteins HuR and PARN [Poly(A) specific ribonuclease deadenylase]. HuR and PARN destabilize Ctn RNA in absence of ADAR2, indicating that ADAR2 stabilizes Ctn RNA by antagonizing its degradation by PARN and HuR. Transcriptomic analysis identified other RNAs that are regulated by a similar mechanism. In summary, we identify a regulatory mechanism whereby ADAR2 enhances target RNA stability by limiting the interaction of RNA-destabilizing proteins with their cognate substrates.","claims":[{"public_id":"cl_1bc7259d2e3269f66b3e9cfe2b9ce023","status":"active","text":"ADAR2 stabilizes a subset of transcripts by limiting the interaction of RNA-destabilizing proteins HuR and PARN with their cognate substrates.","confidence":0.9,"contributors":[{"id":32,"public_id":"7c402c1b98","public_label":"뀨 (7c402c1b98)","roles":["extraction"],"url":"https://sah.borca.ai/u/7c402c1b98"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_1bc7259d2e3269f66b3e9cfe2b9ce023"},{"public_id":"cl_fcd786d7259461537021bf17f4ba7b33","status":"active","text":"ADAR2-mediated stabilization of Ctn RNA occurs in an editing-independent manner.","confidence":0.85,"contributors":[{"id":32,"public_id":"7c402c1b98","public_label":"뀨 (7c402c1b98)","roles":["extraction"],"url":"https://sah.borca.ai/u/7c402c1b98"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_fcd786d7259461537021bf17f4ba7b33"},{"public_id":"cl_9bade50ff246fe3f3d228648b3d740e0","status":"active","text":"In the absence of ADAR2, the abundance and half-life of Ctn RNA are significantly reduced.","confidence":0.9,"contributors":[{"id":32,"public_id":"7c402c1b98","public_label":"뀨 (7c402c1b98)","roles":["extraction"],"url":"https://sah.borca.ai/u/7c402c1b98"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_9bade50ff246fe3f3d228648b3d740e0"},{"public_id":"cl_60a7243e26989771d984b75c83c95d4d","status":"active","text":"Unedited Ctn RNA shows enhanced interaction with HuR and PARN, which destabilize Ctn RNA in the absence of ADAR2.","confidence":0.85,"contributors":[{"id":32,"public_id":"7c402c1b98","public_label":"뀨 (7c402c1b98)","roles":["extraction"],"url":"https://sah.borca.ai/u/7c402c1b98"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_60a7243e26989771d984b75c83c95d4d"}],"concepts":[{"public_id":"co_2acc1b48c79faf3915b9661c2c41a754","status":"active","name":"HuR","description":"An RNA-binding protein that destabilizes Ctn RNA in the absence of ADAR2.","types":["protein","RNA-binding protein"],"aliases":[],"contributors":[{"id":32,"public_id":"7c402c1b98","public_label":"뀨 (7c402c1b98)","roles":["extraction"],"url":"https://sah.borca.ai/u/7c402c1b98"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_2acc1b48c79faf3915b9661c2c41a754"},{"public_id":"co_2c855592ab4f85ac2d20d61ec8220c40","status":"active","name":"PARN","description":"Poly(A) specific ribonuclease deadenylase that destabilizes Ctn RNA in the absence of ADAR2.","types":["protein","enzyme"],"aliases":["Poly(A) specific ribonuclease deadenylase"],"contributors":[{"id":32,"public_id":"7c402c1b98","public_label":"뀨 (7c402c1b98)","roles":["extraction"],"url":"https://sah.borca.ai/u/7c402c1b98"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_2c855592ab4f85ac2d20d61ec8220c40"},{"public_id":"co_73b066c2f76e71e3e91b9005edbee670","status":"active","name":"RNA half-life","description":"The measure of Ctn RNA stability, which is reduced in the absence of ADAR2.","types":["measurement","property"],"aliases":["half-life"],"contributors":[{"id":32,"public_id":"7c402c1b98","public_label":"뀨 (7c402c1b98)","roles":["extraction"],"url":"https://sah.borca.ai/u/7c402c1b98"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_73b066c2f76e71e3e91b9005edbee670"},{"public_id":"co_7cea6bdefc7317e30fe2c3e2e307ea59","status":"active","name":"ADAR2","description":"Adenosine deaminase acting on RNA that catalyzes A-to-I editing and stabilizes RNA by limiting access of decay-promoting proteins.","types":["protein","enzyme"],"aliases":[],"contributors":[{"id":32,"public_id":"7c402c1b98","public_label":"뀨 (7c402c1b98)","roles":["extraction"],"url":"https://sah.borca.ai/u/7c402c1b98"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_7cea6bdefc7317e30fe2c3e2e307ea59"},{"public_id":"co_9977ecd521e8ed207dea5868dc01dc2c","status":"active","name":"unedited Ctn RNA","description":"Ctn RNA that has not undergone A-to-I editing by ADAR2 and shows enhanced interaction with HuR and PARN.","types":["RNA","substrate"],"aliases":[],"contributors":[{"id":32,"public_id":"7c402c1b98","public_label":"뀨 (7c402c1b98)","roles":["extraction"],"url":"https://sah.borca.ai/u/7c402c1b98"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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