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.

APOBEC3B: Pathological consequences of an innate immune DNA mutator

“…First, many of the APOBEC3s have been described to defend against a diverse array of viral pathogens, including retroviruses, hepatitis viruses, papillomaviruses, and others. [20][21][22][23][24] Of note, APOBEC3D, F, G, and H have been shown to restrict HIV-1 replication by deaminating cDNA intermediates that normally occur during the HIV-1 life cycle. [25,26] Second, several APOBEC3s, including APOBEC3A, B, and F, have been shown to inhibit retrotransposition of L1 and Alu elements in human cells.…”

Mouse knockout models for HIV-1 restriction factors

“…They constitute a family of 11 members in humans and 5 in mice [120, 121]. The family can be divided into five subgroups: AID and APOBEC1-4 [120].…”

“…AID proteins introduce mutations into immunoglobulin genes and thereby contribute to antibody diversification [122]. APOBEC1 edits a specific messenger RNA and changes its coding potential, while little is known about APOBEC2 and -4 [120, 121]. The APOBEC3 subfamily and in some species APOBEC1 are involved in cell-intrinsic antiviral host defence and in the control of retroelements [121, 123].…”

“…APOBEC1 edits a specific messenger RNA and changes its coding potential, while little is known about APOBEC2 and -4 [120, 121]. The APOBEC3 subfamily and in some species APOBEC1 are involved in cell-intrinsic antiviral host defence and in the control of retroelements [121, 123]. In particular, APOBEC3G has been studied in detail and can be considered as the first described HIV-1 restriction factor [4, 5, 123].…”

Insights from human congenital disorders of intestinal lipid metabolism

“…It produces two forms of circulating Apo B, namely Apo B-48 (2,152 amino acids) and Apo B-100 (4,536 amino acids), by a unique mRNA editing process (147)(148)(149). This RNA editing mechanism converts a codon (CAA) in the human intestine to a translation stop codon (UAA) at 48% of the full-length coding sequence.…”