title: Functional requirements of AID's higher order structures and their interaction with RNA-binding proteins.
abstract: Activation-induced cytidine deaminase (AID) is essential for the somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes. Although both the N and C termini of AID have unique functions in DNA cleavage and recombination, respectively, during SHM and CSR, their molecular mechanisms are poorly understood. Using a bimolecular fluorescence complementation (BiFC) assay combined with glycerol gradient fractionation, we revealed that the AID C terminus is required for a stable dimer formation. Furthermore, AID monomers and dimers form complexes with distinct heterogeneous nuclear ribonucleoproteins (hnRNPs). AID monomers associate with DNA cleavage cofactor hnRNP K whereas AID dimers associate with recombination cofactors hnRNP L, hnRNP U, and Serpine mRNA-binding protein 1. All of these AID/ribonucleoprotein associations are RNA-dependent. We propose that AID's structure-specific cofactor complex formations differentially contribute to its DNA-cleavage and recombination functions.
authors.affiliation: Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Samiran
authors.initials: S
authors.lastname: Mondal
authors.affiliation: Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Nasim A
authors.initials: NA
authors.lastname: Begum
authors.affiliation: Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-ku, Kyoto 606-8501, Japan honjo@mfour.med.kyoto-u.ac.jp.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
mesh_terms: D000818:Animals; D003564:Cytidine Deaminase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D005990:Glycerol / Q000737:chemistry; D057809:HEK293 Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008817:Mice, Mutant Strains; D009154:Mutation; D025941:Protein Interaction Mapping / Q000379:methods; D055503:Protein Multimerization; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D011995:Recombination, Genetic; D013329:Structure-Activity Relationship; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D016601:RNA-Binding Proteins; D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase; D005990:Glycerol
keywords: AID; APOBEC; BiFC; SERBP1; hnRNP U