http://purl.uniprot.org/citations/37094168 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/37094168 | http://www.w3.org/2000/01/rdf-schema#comment | "Activation-induced cytidine deaminase (AID) is the essential enzyme for imprinting immunological memory through class switch recombination (CSR) and somatic hypermutation (SHM) of the immunoglobulin (Ig) gene. AID-dependent reduction of Topoisomerase 1 (Top1) promotes DNA cleavage that occurs upon Ig gene diversification, whereas the mechanism behind AID-induced Top1 reduction remains unclear. Here, we clarified the contribution of the microRNA-Ago2 complex in AID-dependent Top1 decrease. Ago2 binds to Top1 3'UTR with two regions of AID-dependent Ago2-binding sites (5'- and 3'dABs). Top1 3'UTR knockout (3'UTRKO) in B lymphoma cells leads to decreases in DNA break efficiency in the IgH gene accompanied by a reduction in CSR and SHM frequencies. Furthermore, AID-dependent Top1 protein reduction and Ago2-binding to Top1 mRNA are down-regulated in 3'UTRKO cells. Top1 mRNA in the highly translated fractions of the sucrose gradient is decreased in an AID-dependent and Top1 3'UTR-mediated manner, resulting in a decrease in Top1 protein synthesis. Both AID and Ago2 localize in the mRNA-binding protein fractions and they interact with each other. Furthermore, we found some candidate miRNAs which possibly bind to 5'- and 3'dAB in Top1 mRNA. Among them, miR-92a-3p knockdown induces the phenotypes of 3'UTRKO cells to wild-type cells whereas it does not impact on 3'UTRKO cells. Taken together, the Ago2-miR-92a-3p complex will be recruited to Top1 3'UTR in an AID-dependent manner and posttranscriptionally reduces Top1 protein synthesis. These consequences cause the increase in a non-B-DNA structure, enhance DNA cleavage by Top1 in the Ig gene and contribute to immunological memory formation."xsd:string |
http://purl.uniprot.org/citations/37094168 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.2216918120"xsd:string |
http://purl.uniprot.org/citations/37094168 | http://purl.uniprot.org/core/author | "Kobayashi M."xsd:string |
http://purl.uniprot.org/citations/37094168 | http://purl.uniprot.org/core/author | "Matsuda F."xsd:string |
http://purl.uniprot.org/citations/37094168 | http://purl.uniprot.org/core/author | "Shimizu M."xsd:string |
http://purl.uniprot.org/citations/37094168 | http://purl.uniprot.org/core/author | "Wakaguri H."xsd:string |
http://purl.uniprot.org/citations/37094168 | http://purl.uniprot.org/core/author | "Honjo T."xsd:string |
http://purl.uniprot.org/citations/37094168 | http://purl.uniprot.org/core/author | "Higasa K."xsd:string |
http://purl.uniprot.org/citations/37094168 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
http://purl.uniprot.org/citations/37094168 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
http://purl.uniprot.org/citations/37094168 | http://purl.uniprot.org/core/pages | "e2216918120"xsd:string |
http://purl.uniprot.org/citations/37094168 | http://purl.uniprot.org/core/title | "Ago2 and a miRNA reduce Topoisomerase 1 for enhancing DNA cleavage in antibody diversification by activation-induced cytidine deaminase."xsd:string |
http://purl.uniprot.org/citations/37094168 | http://purl.uniprot.org/core/volume | "120"xsd:string |
http://purl.uniprot.org/citations/37094168 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/37094168 |
http://purl.uniprot.org/citations/37094168 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/37094168 |
http://purl.uniprot.org/uniprot/#_Q3ULF5-mappedCitation-37094168 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37094168 |
http://purl.uniprot.org/uniprot/#_Q04750-mappedCitation-37094168 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37094168 |
http://purl.uniprot.org/uniprot/#_Q3UQ34-mappedCitation-37094168 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37094168 |
http://purl.uniprot.org/uniprot/#_Q8CGT9-mappedCitation-37094168 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37094168 |
http://purl.uniprot.org/uniprot/#_Q3TSR2-mappedCitation-37094168 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37094168 |
http://purl.uniprot.org/uniprot/#_Q3TUS4-mappedCitation-37094168 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37094168 |
http://purl.uniprot.org/uniprot/#_Q569Q5-mappedCitation-37094168 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37094168 |
http://purl.uniprot.org/uniprot/#_Q3TPX7-mappedCitation-37094168 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37094168 |
http://purl.uniprot.org/uniprot/#_Q6P239-mappedCitation-37094168 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37094168 |