Differential inhibition of LINE1 and LINE2 retrotransposition by vertebrate AID/APOBEC proteins

Nataša Lindič,Nika Lovšin,Maruška Budič,Binyamin A Knisbacher,Toni Petan,Erez Y Levanon

doi:10.1186/1742-4690-10-156

Nataša Lindič, Nika Lovšin + Show 4 more

Open Access

https://doi.org/10.1186/1742-4690-10-156

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Abstract

BackgroundThe role of AID/APOBEC proteins in the mammalian immune response against retroviruses and retrotransposons is well established. G to A hypermutations, the hallmark of their cytidine deaminase activity, are present in several mammalian retrotransposons. However, the role of AID/APOBEC proteins in non-mammalian retroelement restriction is not completely understood.ResultsHere we provide the first evidence of anti-retroelement activity of a reptilian APOBEC protein. The green anole lizard A1 protein displayed potent DNA mutator activity and inhibited ex vivo retrotransposition of LINE1 and LINE2 ORF1 protein encoding elements, displaying a mechanism of action similar to that of the human A1 protein. In contrast, the human A3 proteins did not require ORF1 protein to inhibit LINE retrotransposition, suggesting a differential mechanism of anti-LINE action of A1 proteins, which emerged in amniotes, and A3 proteins, exclusive to placental mammals. In accordance, genomic analyses demonstrate differential G to A DNA editing of LINE retrotransposons in the lizard genome, which is also the first evidence for G to A DNA editing in non-mammalian genomes.ConclusionOur data suggest that vertebrate APOBEC proteins differentially inhibit the retrotransposition of LINE elements and that the anti-retroelement activity of APOBEC proteins predates mammals.

Highlights

The role of activation-induced deaminase (AID)/APOBEC proteins in the mammalian immune response against retroviruses and retrotransposons is well established
Lizard A1 protein inhibits human L1 (hL1) and zebrafish L2-1 (ZfL2-1), but not zebrafish L2-2 (ZfL2-2), retrotransposons The cytidine deaminases (CDA) activity of the zebrafish AID protein and its weak but present anti-retroelement activity, observed against the hL1 element [56], suggest that zebrafish APOBEC proteins could act as inhibitors of retrotransposition, in particular against zebrafish elements
The zebrafish A2a, A2b and AID proteins had no effect on the retrotransposition of the zebrafish L2-1 (ZfL2-1) or L2-2 (ZfL2-2) elements, with A2a and AID displaying only a very weak inhibitory effect against the hL1 element (Additional file 1: Figure S2)

Summary

Introduction

The role of AID/APOBEC proteins in the mammalian immune response against retroviruses and retrotransposons is well established. The L2 retrotransposons can AID/APOBEC protein family members are cytidine deaminases (CDA) that convert cytidine to uridine in DNA and RNA [23]. It has been shown that the lizard A1 protein possesses DNA deaminase activity [24], which is consistent with the hypothesis that the original function of AID/APOBEC family of enzymes is retroelement restriction, rather than antibody diversification [59]

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