title: The splicing regulator PTBP2 interacts with the cytidine deaminase AID and promotes binding of AID to switch-region DNA.
abstract: During immunoglobulin class-switch recombination (CSR), the cytidine deaminase AID induces double-strand breaks into transcribed, repetitive DNA elements called switch sequences. The mechanism that promotes the binding of AID specifically to switch regions remains to be elucidated. Here we used a proteomic screen with in vivo biotinylation of AID to identify the splicing regulator PTBP2 as a protein that interacts with AID. Knockdown of PTBP2 mediated by short hairpin RNA in B cells led to a decrease in binding of AID to transcribed switch regions, which resulted in considerable impairment of CSR. PTBP2 is thus an effector of CSR that promotes the binding of AID to switch-region DNA.
authors.affiliation: Graduate Program in Immunology and Microbial Pathogenesis, Weill-Cornell Medical School, New York, New York, USA.
authors.forename: Urszula
authors.initials: U
authors.lastname: Nowak
authors.forename: Allysia J
authors.initials: AJ
authors.lastname: Matthews
authors.forename: Simin
authors.initials: S
authors.lastname: Zheng
authors.forename: Jayanta
authors.initials: J
authors.lastname: Chaudhuri
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007134:Immunoglobulin Switch Region / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics / Q000276:immunology; D019076:Transgenes / Q000235:genetics; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D009419:Nerve Tissue Proteins; C429773:Ptbp2 protein, mouse; D034741:RNA, Small Interfering; D038941:Polypyrimidine Tract-Binding Protein; D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase