AID can restrict L1 retrotransposition suggesting a dual role in innate and adaptive immunity

Donna A. Macduff, Zachary L. Demorest, Reuben S. Harris

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Retrotransposons make up over 40% of the mammalian genome. Some copies are still capable of mobilizing and new insertions promote genetic variation. Several members of the APOBEC3 family of DNA cytosine deaminases function to limit the replication of a variety of retroelements, such as the long-terminal repeat (LTR)-containing MusD and Ty1 elements, and that of the non-LTR retrotransposons, L1 and Alu. However, the APOBEC3 genes are limited to mammalian lineages, whereas retrotransposons are far more widespread. This raises the question of what cellular factors control retroelement transposition in species that lack APOBEC3 genes. A strong phylogenetic case can be made that an ancestral activation-induced deaminase (AID)-like gene duplicated and diverged to root the APOBEC3 lineage in mammals. Therefore, we tested the hypothesis that present-day AID proteins possess anti-retroelement activity. We found that AID can inhibit the retrotransposition of L1 through a DNA deamination-independent mechanism. This mechanism may manifest in the cytoplasmic compartment co- or posttranslationally. Together with evidence for AID expression in the ovary, our data combined to suggest that AID has innate immune functions in addition to its integral roles in creating antibody diversity.

Original languageEnglish (US)
Pages (from-to)1854-1867
Number of pages14
JournalNucleic acids research
Volume37
Issue number6
DOIs
StatePublished - 2009

Bibliographical note

Funding Information:
National Institutes of Health (AI064046 and GM090437); University of Minnesota Leukemia Research Fund (to R.S.H.); University of Minnesota Graduate School Doctoral Dissertation Fellowship (to D.A.M.). Funding for open access charge: National Institute of General Medical Sciences, National Institutes of Health, Bethesda, Maryland (GM090437).

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