title: Apolipoprotein B mRNA-editing, catalytic polypeptide cytidine deaminases and retroviral restriction.
abstract: Apolipoprotein B (apo B) messenger RNA (mRNA)-editing, catalytic polypeptide (APOBEC) cytidine deaminases (CDAs), which can insert mutations into DNA and/or RNA as a result of their ability to deaminate cytidine (C) to uridine (U), originated from a branch of the zinc-dependent deaminase superfamily at the beginning of vertebrate radiation. The ability of mammalian CDAs encoded by the APOBEC3 genes to restrict a broad number of endogenous retroelements and exogenous retroviruses, including human immunodeficiency virus-1, is well established. Furthermore, APOBEC1 from a variety of mammalian species, which mediates the C-to-U deamination of apo B mRNA, a protein involved in lipid transport, also has a role in controlling mobile elements. A large portion of the mammalian genome is derived from ancient transposable elements. Retroelements, transported by an intracellular copy-and-paste process involving an RNA intermediate, constitute the majority of these mobile genetic elements. Endogenous retroviruses are long-terminal repeat (LTR)-type retroelements that account for approximately 10% of human and murine genomic DNA. Non-LTR members are present in extremely high copy numbers, with approximately 40% of the human and murine genomes consisting of long-interspersed nuclear element-1 (L1). These L1 elements modify mammalian genomes not only through insertions but also by the indirect replication of non-autonomous retrotransposons. As expected, vertebrate intrinsic immunity has evolved to support a balance between retroelement insertions that cause deleterious gene disruptions and those that confer beneficial genetic diversity. This review discusses the current understanding of the mechanism of action of APOBEC CDAs and their role in controlling retroviruses and retroelements.
authors.affiliation: Department of Retrovirology and Self-Defense, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. akoito@kumamoto-u.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Koito
authors.forename: Terumasa
authors.initials: T
authors.lastname: Ikeda
mesh_terms: D000071479:APOBEC-1 Deaminase; D000818:Animals; D003564:Cytidine Deaminase / Q000378:metabolism*; D006801:Humans; D018626:Retroelements; D012190:Retroviridae / Q000378:metabolism*
chemical_list: D018626:Retroelements; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D003564:Cytidine Deaminase