title: RNA Exosome Regulates AID DNA Mutator Activity in the B Cell Genome.
abstract: The immunoglobulin diversification processes of somatic hypermutation and class switch recombination critically rely on transcription-coupled targeting of activation-induced cytidine deaminase (AID) to Ig loci in activated B lymphocytes. AID catalyzes deamination of cytidine deoxynucleotides on exposed single-stranded DNA. In addition to driving immunoglobulin diversity, promiscuous targeting of AID mutagenic activity poses a deleterious threat to genomic stability. Recent genome-wide studies have uncovered pervasive AID activity throughout the B cell genome. It is increasingly apparent that AID activity is frequently targeted to genomic loci undergoing early transcription termination where RNA exosome promotes the resolution of stalled transcription complexes via cotranscriptional RNA degradation mechanisms. Here, we review aspects and consequences of eukaryotic transcription that lead to early termination, RNA exosome recruitment, and ultimately targeting of AID mutagenic activity.
authors.affiliation: Department of Microbiology & Immunology, College of Physicians and Surgeons, Columbia University, New York, USA. Electronic address: evangelos.pefanis@regeneron.com.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Pefanis
authors.affiliation: Department of Microbiology & Immunology, College of Physicians and Surgeons, Columbia University, New York, USA. Electronic address: ub2121@columbia.edu.
authors.forename: Uttiya
authors.initials: U
authors.lastname: Basu
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D003564:Cytidine Deaminase / Q000378:metabolism*; D063326:Exosome Multienzyme Ribonuclease Complex / Q000378:metabolism*; D042822:Genomic Instability; D006801:Humans; D016296:Mutagenesis; D014158:Transcription, Genetic
chemical_list: D063326:Exosome Multienzyme Ribonuclease Complex; D003564:Cytidine Deaminase
keywords: Activation-induced cytidine deaminase; Antisense RNA; B lymphocytes; Noncoding RNA; RNA exosome; Somatic hypermutation; Transcription termination