APOBEC3DE Inhibits LINE-1 Retrotransposition by Interacting with ORF1p and Influencing LINE Reverse Transcriptase Activity

Liang, Weifang; Xu, Junwei; Yuan, Wei; Song, Xuan; Zhang, Jianyong; Wei, Wei; Yu, Xiao Fang; Yang, Ying

doi:10.1371/journal.pone.0157220

Cited by 34 publications

(40 citation statements)

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“…A3DE is expressed in hESC, associates with ORF1p protein in an RNAdependent manner and this interaction causes a strong inhibition of the ORF2p RT activity (Liang et al 2016). The authors showed also a weak RNA-dependent interaction between A3B and ORF1p, but failed to observe any effect of this enzyme on ORF2p activity, thus suggesting a different inhibitory mechanism.…”

Section: Inhibition Of Line-1 and Alu Retrotransposition Mediated By mentioning

confidence: 95%

“…Several members of the AID/APOBEC family (AID, A1, A3A, A3B, A3C, A3DE, A3F and A3H) were shown to inhibit both LINE-1 and Alu retrotransposition (Pizarro and Cristofari 2016;Bogerd et al 2006;Muckenfuss et al 2006;Chen et al 2006;Stenglein and Harris 2006;Kinomoto et al 2007;Niewiadomska et al 2007;Richardson et al 2014;Koyama et al 2013;Horn et al 2014;Liang et al 2016;Feng et al 2017;Ikeda et al 2011). The majority of these experiments were carried out in cell cultures and the inhibition was found to be mainly mediated by editing-independent mechanisms (Pizarro and Cristofari 2016).…”

Section: Inhibition Of Line-1 and Alu Retrotransposition Mediated By mentioning

confidence: 99%

“…Very recently, Liang and collaborators showed that A3DE, like A3B, potently inhibits L1 retrotransposition in 293 T cells (Liang et al 2016). A3DE is expressed in hESC, associates with ORF1p protein in an RNAdependent manner and this interaction causes a strong inhibition of the ORF2p RT activity (Liang et al 2016).…”

Section: Inhibition Of Line-1 and Alu Retrotransposition Mediated By mentioning

confidence: 99%

“…This is an interesting observation, since APOBEC and ADAR enzymes regulate viral replication and/or infection using both deaminasedependent and -independent mechanisms, and APOBEC enzymes extensively mutate LTR retrotransposons (Salter et al 2016;Samuel 2011;Levanon 2015, 2016). Of note, ADAR1 and some APOBEC proteins associate with L1 RNAs (A1 and A3DE; Ikeda et al 2011;Liang et al 2016). It would be of great interest to test whether this is true for all the family members.…”

Section: Inhibition Of Line-1 and Alu Retrotransposition Mediated By mentioning

confidence: 99%

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Post-transcriptional regulation of LINE-1 retrotransposition by AID/APOBEC and ADAR deaminases

et al. 2018

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Long interspersed element-1 (LINE-1 or L1) retrotransposons represent the only functional family of autonomous transposable elements in humans and formed 17% of our genome. Even though most of the human L1 sequences are inactive, a limited number of copies per individual retain the ability to mobilize by a process termed retrotransposition. The ongoing L1 retrotransposition may result in insertional mutagenesis that could lead to negative consequences such as genetic disease and cancer. For this reason, cells have evolved several mechanisms of defense to restrict L1 activity. Among them, a critical role for cellular deaminases [activation-induced deaminase (AID)/apolipoprotein B mRNA-editing catalytic polypeptide-like (APOBEC) and adenosine deaminases that act on RNA (ADAR) enzymes] has emerged. The majority of the AID/ APOBEC family of proteins are responsible for the deamination of cytosine to uracil (C-to-U editing) within DNA and RNA targets. The ADARs convert adenosine bases to inosines (A-to-I editing) within doublestranded RNA (dsRNA) targets. This review will discuss the current understanding of the regulation of LINE-1 retrotransposition mediated by these enzymes.

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Section: Inhibition Of Line-1 and Alu Retrotransposition Mediated By mentioning

confidence: 95%

Section: Inhibition Of Line-1 and Alu Retrotransposition Mediated By mentioning

confidence: 99%

Section: Inhibition Of Line-1 and Alu Retrotransposition Mediated By mentioning

confidence: 99%

Section: Inhibition Of Line-1 and Alu Retrotransposition Mediated By mentioning

confidence: 99%

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Post-transcriptional regulation of LINE-1 retrotransposition by AID/APOBEC and ADAR deaminases

et al. 2018

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“…First, since A3 enzymes bind RNA with high affinity, it was thought that the A3 enzymes would act as a roadblock to reverse transcription. Similarly, A3s could bind the LINE-1 RNA in the cytoplasm and cause it to accumulate in cytoplasmic RNA processing bodies (P-bodies), preventing nuclear import [167,168]. DNA sequencing of integrated LINE-1 genomes had little evidence of cytosine deamination, which supports these mechanisms mediated by RNA binding.…”

Section: Restriction Of Endogenous Retroelements By Apobec3mentioning

confidence: 92%

Biochemical Basis of APOBEC3 Deoxycytidine Deaminase Activity on Diverse DNA Substrates

2018

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Apolipoprotein B mRNA-editing enzyme-catalytic, polypeptide-like 3 (APOBEC3) enzymes are a family of single-stranded (ss)DNA cytosine deaminases that serve as a host restriction factors for retrotransposons and viruses that contain a ssDNA intermediate. While the APOBEC3 family was originally expanded to restrict endogenous retroelements, the majority of these targets are now inactivated and the family has been found to act on different targets, such as viral ssDNA as a mechanism of viral defense. Some of the family members also catalyze "offtarget" deaminations in human ssDNA and have been implicated in somatic mutagenesis that can lead to cancer.My PhD thesis research investigated the biochemical mechanisms underlying both the benefits and the risks of the A3 family of enzymes. The central hypothesis of this work is that A3 enzymes have evolved distinct biochemical mechanisms to deaminate ssDNA that differentiate A3 restriction of retroelements and retroviruses from A3-induced somatic mutagenesis.Therefore, we investigated the biochemical mechanisms the A3 enzymes utilize during restriction of Human Immunodeficiency Virus (HIV) in both deamination-dependent and deaminationindependent modes, as well as the unique mechanisms employed during mutation of genomic DNA. There are seven APOBEC3 members (A-H, excluding E) and of these, four members (A3D, A3F, A3G, A3H) have been identified to restrict HIV replication in CD4 T+ cells, and currently three members (A3A, A3B and A3H haplotype I) have been implicated in somatic mutagenesis.The APOBEC3 enzymes that restrict HIV replication function optimally in the absence of the HIV viral infectivity factor (Vif). Vif targets APOBEC3 for degradation via the proteasome in HIV infected cells. For APOBEC3s that are able to fortuitously escape Vif mediated degradation and become encapsidated, the enzymes can deaminate cytosines to form uracils in viral (-)DNA. Replication of (-)DNA to (+)DNA causes HIV-1 reverse transcriptase to incorporate adenines opposite uracils which creates C/G→T/A transition mutations. While restriction of HIV most commonly occurs through this deamination-dependent mechanism, APOBEC3s have also been identified to interfere with HIV reverse transcriptase processes in a deamination-independent manner, although this mechanism is secondary to the deaminationdependent mode. In order to restrict retroelements and viruses such as HIV, the A3 enzymes iii require an efficient processive ssDNA scanning mechanism that allows them to search for, and locate cytosines on ssDNA in the finite amount of time the substrate is available during formation of the double-stranded DNA provirus. To understand if this requirement was lost in A3 enzymes unable to restrict HIV, we studied A3C. Human A3C is not able to restrict HIV, in comparison to the more active gorilla and chimpanzee A3C orthologs that can restrict HIV, however an explanation for this difference was lacking. A polymorphism, S188I, in human A3C, which is found in less than 3% of the global population lead...

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An update on post‐transcriptional regulation of retrotransposons

Warkocki

2022

FEBS Letters

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Retrotransposons, including LINE-1, Alu, SVA, and endogenous retroviruses, are one of the major constituents of human genomic repetitive sequences. Through the process of retrotransposition, some of them occasionally insert into new genomic locations by a copy-paste mechanism involving RNA intermediates. Irrespective of de novo genomic insertions, retrotransposon expression can lead to DNA double-strand breaks and stimulate cellular innate immunity through endogenous patterns. As a result, retrotransposons are tightly regulated by multi-layered regulatory processes to prevent the dangerous effects of their expression. In recent years, significant progress was made in revealing how retrotransposon biology intertwines with general posttranscriptional RNA metabolism. Here, I summarize current knowledge on the involvement of post-transcriptional factors in the biology of retrotransposons, focusing on LINE-1. I emphasize general RNA metabolisms such as methylation of adenine (m 6 A), RNA 3 0 -end polyadenylation and uridylation, RNA decay and translation regulation. I discuss the effects of retrotransposon RNP sequestration in cytoplasmic bodies and autophagy. Finally, I summarize how innate immunity restricts retrotransposons and how retrotransposons make use of cellular enzymes, including the DNA repair machinery, to complete their replication cycles.

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APOBEC3DE Inhibits LINE-1 Retrotransposition by Interacting with ORF1p and Influencing LINE Reverse Transcriptase Activity

Cited by 34 publications

References 51 publications

Post-transcriptional regulation of LINE-1 retrotransposition by AID/APOBEC and ADAR deaminases

Post-transcriptional regulation of LINE-1 retrotransposition by AID/APOBEC and ADAR deaminases

Biochemical Basis of APOBEC3 Deoxycytidine Deaminase Activity on Diverse DNA Substrates

An update on post‐transcriptional regulation of retrotransposons

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