title: RNA Exosome and Non-coding RNA-Coupled Mechanisms in AID-Mediated Genomic Alterations.
abstract: The eukaryotic RNA exosome is a well-conserved protein complex with ribonuclease activity implicated in RNA metabolism. Various families of non-coding RNAs have been identified as substrates of the complex, underscoring its role as a non-coding RNA processing/degradation unit. However, the role of RNA exosome and its RNA processing activity on DNA mutagenesis/alteration events have not been investigated until recently. B lymphocytes use two DNA alteration mechanisms, class switch recombination (CSR) and somatic hypermutation (SHM), to re-engineer their antibody gene expressing loci until a tailored antibody gene for a specific antigen is satisfactorily generated. CSR and SHM require the essential activity of the DNA activation-induced cytidine deaminase (AID). Causing collateral damage to the B-cell genome during CSR and SHM, AID induces unwanted (and sometimes oncogenic) mutations at numerous non-immunoglobulin gene sequences. Recent studies have revealed that AID's DNA mutator activity is regulated by the RNA exosome complex, thus providing an example of a mechanism that relates DNA mutagenesis to RNA processing. Here, we review the emergent functions of RNA exosome during CSR, SHM, and other chromosomal alterations in B cells, and discuss implications relevant to mechanisms that maintain B-cell genomic integrity.
authors.affiliation: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Brice
authors.initials: B
authors.lastname: Laffleur
authors.affiliation: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: ub2121@cumc.columbia.edu.
authors.forename: Uttiya
authors.initials: U
authors.lastname: Basu
authors.affiliation: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Lim
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D002869:Chromosome Aberrations; D003564:Cytidine Deaminase / Q000378:metabolism; D055354:Exosomes / Q000235:genetics*; D006801:Humans; D017578:Immunoglobulin Class Switching; D009154:Mutation; D012323:RNA Processing, Post-Transcriptional; D022661:RNA, Untranslated / Q000235:genetics*; D027041:Somatic Hypermutation, Immunoglobulin; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D022661:RNA, Untranslated; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: AID; Class switch recombination; Genome integrity; RNA exosome; Somatic hypermutation