Article
Cellular inhibitors of long interspersed element 1 and Alu retrotransposition.
Center for Virology and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Proceedings of the National Academy of Sciences (impact factor:
9.68).
07/2006;
103(23):8780-5.
DOI:10.1073/pnas.0603313103
Source: PubMed
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Article: The innate antiretroviral factor APOBEC3G does not affect human LINE-1 retrotransposition in a cell culture assay.
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ABSTRACT: APOBEC3G (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G) is an innate intracellular antiretroviral factor that can inhibit viral retroelements such as retroviruses and hepadnaviruses. However, it is unknown whether it can act on non-viral substrates. Retrotransposons are transposable elements that cumulatively account for about one third of the human genome. They are commonly classified in long terminal repeat (LTR) retrotransposons, which are strongly homologous to retroviruses, and non-LTR retrotransposons also known as L1 elements or LINE-1 (long interspersed nucleotide element-1) elements. Most of the L1 elements are defective and only a small number are very active in vivo, but they are responsible for nearby all of the retrotransposition in the human population. The cloning of active human L1 elements has allowed the development of tissue culture-based assays for measuring their retrotransposition potential. We used such an assay to demonstrate that APOBEC3G, which impairs the replication of exogenous retroelements, does not affect the replication of endogenous L1 retrotransposons.Journal of Biological Chemistry 11/2004; 279(42):43371-3. · 4.77 Impact Factor -
Article: APOBEC3A is a potent inhibitor of adeno-associated virus and retrotransposons.
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ABSTRACT: APOBEC3 proteins constitute a family of cytidine deaminases that provide intracellular resistance to retrovirus replication and transposition of endogenous retroelements. One family member, APOBEC3A (hA3A), is an orphan, without any known antiviral activity. We show that hA3A is catalytically active and that it, but none of the other family members, potently inhibits replication of the parvovirus adeno-associated virus (AAV). hA3A was also a potent inhibitor of the endogenous LTR retroelements, MusD, IAP, and the non-LTR retroelement, LINE-1. Its function was dependent on the conserved amino acids of the hA3A active site, consistent with a role for cytidine deamination, although mutations in retroelement sequences were not found. These findings demonstrate the potent activity of hA3A, an APOBEC3 family member with no previously identified function. They also highlight the functional differences between APOBEC3 proteins. The APOBEC3 family members have distinct functions and may have evolved to resist various classes of genetic elements.Current Biology 04/2006; 16(5):480-5. · 9.65 Impact Factor -
Article: An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22.
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ABSTRACT: The cytidine (C) to uridine (U) editing of apolipoprotein (apo) B mRNA is mediated by tissue-specific, RNA-binding cytidine deaminase APOBEC1. APOBEC1 is structurally homologous to Escherichia coli cytidine deaminase (ECCDA), but has evolved specific features required for RNA substrate binding and editing. A signature sequence for APOBEC1 has been used to identify other members of this family. One of these genes, designated APOBEC2, is found on chromosome 6. Another gene corresponds to the activation-induced deaminase (AID) gene, which is located adjacent to APOBEC1 on chromosome 12. Seven additional genes, or pseudogenes (designated APOBEC3A to 3G), are arrayed in tandem on chromosome 22. Not present in rodents, this locus is apparently an anthropoid-specific expansion of the APOBEC family. The conclusion that these new genes encode orphan C to U RNA-editing enzymes of the APOBEC family comes from similarity in amino acid sequence with APOBEC1, conserved intron/exon organization, tissue-specific expression, homodimerization, and zinc and RNA binding similar to APOBEC1. Tissue-specific expression of these genes in a variety of cell lines, along with other evidence, suggests a role for these enzymes in growth or cell cycle control.Genomics 04/2002; 79(3):285-96. · 3.02 Impact Factor
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Keywords
Alu reverse transcription
APOBEC3 family
APOBEC3 protein family
APOBEC3A
APOBEC3B
element class
endogenous retrotransposons
genomic DNA
human genome
human innate antiretroviral resistance factors
interspersed element
LINE-1
LINE-1 ORF2 protein
nucleus
Representative members
