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

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

doi:10.1186/1742-4690-10-156

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

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

The Mina and Everard Goodman Faculty of Life Sciences

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Background: The 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.Results: Here 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.Conclusion: Our data suggest that vertebrate APOBEC proteins differentially inhibit the retrotransposition of LINE elements and that the anti-retroelement activity of APOBEC proteins predates mammals.

Original language	English
Article number	156
Journal	Retrovirology
Volume	10
Issue number	1
DOIs	https://doi.org/10.1186/1742-4690-10-156
State	Published - 17 Dec 2013

Bibliographical note

Funding Information:
We thank Shai Carmi for his help at the early stage of the project, and Norihiro Okada, John Moran, Bryan Cullen, Boris Matija Peterlin, Rai Kunal, Silvestro Conticello and Yong-Hui Zheng for reagents. We thank Alenka Čopič for critical reading of the manuscript. This work was supported by the Slovenian Research Agency [31952 to NLi, J7-2230, J1-2141 to NLo and MB, J3-4168 to MB and P1-0207 to NLo and TP]. BAK and EYL were supported by the Israel Science foundation [728/10] and by the European Research Council [311257]. Funding for open access charge: 31952 to NLi.

Keywords

AID
APOBEC3
Cytidine deaminase
G to A hypermutation
LINE1
Lizard APOBEC1
ORF1p
Retrotransposon
Zebrafish APOBEC2
Zebrafish LINE2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/1742-4690-10-156

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@article{80329187214542caa89def95edbd2058,

title = "Differential inhibition of LINE1 and LINE2 retrotransposition by vertebrate AID/APOBEC proteins",

abstract = "Background: The 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.Results: Here 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.Conclusion: Our data suggest that vertebrate APOBEC proteins differentially inhibit the retrotransposition of LINE elements and that the anti-retroelement activity of APOBEC proteins predates mammals.",

keywords = "AID, APOBEC3, Cytidine deaminase, G to A hypermutation, LINE1, Lizard APOBEC1, ORF1p, Retrotransposon, Zebrafish APOBEC2, Zebrafish LINE2",

author = "Nata{\v s}a Lindi{\v c} and Maru{\v s}ka Budi{\v c} and Toni Petan and Knisbacher, {Binyamin A.} and Levanon, {Erez Y.} and Nika Lov{\v s}in",

note = "Funding Information: We thank Shai Carmi for his help at the early stage of the project, and Norihiro Okada, John Moran, Bryan Cullen, Boris Matija Peterlin, Rai Kunal, Silvestro Conticello and Yong-Hui Zheng for reagents. We thank Alenka {\v C}opi{\v c} for critical reading of the manuscript. This work was supported by the Slovenian Research Agency [31952 to NLi, J7-2230, J1-2141 to NLo and MB, J3-4168 to MB and P1-0207 to NLo and TP]. BAK and EYL were supported by the Israel Science foundation [728/10] and by the European Research Council [311257]. Funding for open access charge: 31952 to NLi.",

year = "2013",

month = dec,

day = "17",

doi = "10.1186/1742-4690-10-156",

language = "אנגלית",

volume = "10",

journal = "Retrovirology",

issn = "1742-4690",

publisher = "BioMed Central Ltd.",

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TY - JOUR

T1 - Differential inhibition of LINE1 and LINE2 retrotransposition by vertebrate AID/APOBEC proteins

AU - Lindič, Nataša

AU - Budič, Maruška

AU - Petan, Toni

AU - Knisbacher, Binyamin A.

AU - Levanon, Erez Y.

AU - Lovšin, Nika

N1 - Funding Information: We thank Shai Carmi for his help at the early stage of the project, and Norihiro Okada, John Moran, Bryan Cullen, Boris Matija Peterlin, Rai Kunal, Silvestro Conticello and Yong-Hui Zheng for reagents. We thank Alenka Čopič for critical reading of the manuscript. This work was supported by the Slovenian Research Agency [31952 to NLi, J7-2230, J1-2141 to NLo and MB, J3-4168 to MB and P1-0207 to NLo and TP]. BAK and EYL were supported by the Israel Science foundation [728/10] and by the European Research Council [311257]. Funding for open access charge: 31952 to NLi.

PY - 2013/12/17

Y1 - 2013/12/17

N2 - Background: The 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.Results: Here 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.Conclusion: Our data suggest that vertebrate APOBEC proteins differentially inhibit the retrotransposition of LINE elements and that the anti-retroelement activity of APOBEC proteins predates mammals.

AB - Background: The 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.Results: Here 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.Conclusion: Our data suggest that vertebrate APOBEC proteins differentially inhibit the retrotransposition of LINE elements and that the anti-retroelement activity of APOBEC proteins predates mammals.

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KW - APOBEC3

KW - Cytidine deaminase

KW - G to A hypermutation

KW - LINE1

KW - Lizard APOBEC1

KW - ORF1p

KW - Retrotransposon

KW - Zebrafish APOBEC2

KW - Zebrafish LINE2

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C2 - 24344916

SN - 1742-4690

VL - 10

JO - Retrovirology

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

Abstract

Bibliographical note

Keywords

UN SDGs

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