APOBEC: From mutator to editor

Yang, Bei; Li, Xiaosa; Lei, Liqun; Chen, Jia

doi:10.1016/j.jgg.2017.04.009

Cited by 54 publications

(43 citation statements)

References 206 publications

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“…In order to investigate if A3B and/or A3G are enzymatically active in UCC lines, DNA deamination activity assays were performed using cells lysates from the different UCCs transfected with A3B - and A3G -siRNAs as controls ( Figure 4C ). To measure deaminase activity, we applied a qualitative PCR-based in vitro DNA deamination assay to identify C→U conversion in an 80-nt single-stranded DNA substrate harboring the isozyme-specific motif TT C A or CC C A, specifically recognized by A3B or A3G, respectively ( Jaguva Vasudevan et al, 2017 ; Yang et al, 2017 ). Catalytic deamination of C→U in the respective motif creates specific restriction sites, which can be detected by restriction analysis of the PCR product.…”

Section: Resultsmentioning

confidence: 99%

APOBEC3B Activity Is Prevalent in Urothelial Carcinoma Cells and Only Slightly Affected by LINE-1 Expression

et al. 2018

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The most common mutational signature in urothelial carcinoma (UC), the most common type of urinary bladder cancer is assumed to be caused by the misdirected activity of APOBEC3 (A3) cytidine deaminases, especially A3A or A3B, which are known to normally restrict the propagation of exogenous viruses and endogenous retroelements such as LINE-1 (L1). The involvement of A3 proteins in urothelial carcinogenesis is unexpected because, to date, UC is thought to be caused by chemical carcinogens rather than viral activity. Therefore, we explored the relationship between A3 expression and L1 activity, which is generally upregulated in UC. We found that UC cell lines highly express A3B and in some cases A3G, but not A3A, and exhibit corresponding cytidine deamination activity in vitro. While we observed evidence suggesting that L1 expression has a weak positive effect on A3B and A3G expression and A3B promoter activity, neither efficient siRNA-mediated knockdown nor overexpression of functional L1 elements affected catalytic activity of A3 proteins consistently. However, L1 knockdown diminished proliferation of a UC cell line exhibiting robust endogenous L1 expression, but had little impact on a cell line with low L1 expression levels. Our results indicate that UC cells express A3B at levels exceeding A3A levels by far, making A3B the prime candidate for causing genomic mutations. Our data provide evidence that L1 activation constitutes only a minor and negligible factor involved in induction or upregulation of endogenous A3 expression in UC.

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Section: Resultsmentioning

confidence: 99%

APOBEC3B Activity Is Prevalent in Urothelial Carcinoma Cells and Only Slightly Affected by LINE-1 Expression

et al. 2018

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“…Base editing is a quite different and the most recent GE system, which has been widely used for introducing highly predictable and precise single nucleotide substitutions at genomic targets without requiring donor DNA templates, double‐strand breaks (DSBs) or dependence on homology‐directed repair (HDR) and non‐homologous end joining (NHEJ) . Base editing technology is being used in various organisms and cell lines . It has been considered more effective than HDR‐mediated base‐pair substitution .…”

Section: E‐crisp/cas Systemsmentioning

confidence: 99%

“…Base editing technology is being used in various organisms and cell lines . It has been considered more effective than HDR‐mediated base‐pair substitution . To date, several base editing systems, for instance BE3, BE4, Targeted‐AID, and dCpf1‐BE have been used in various organisms including major crops.…”

Section: E‐crisp/cas Systemsmentioning

confidence: 99%

CRISPR/Cas Systems in Genome Editing: Methodologies and Tools for sgRNA Design, Off‐Target Evaluation, and Strategies to Mitigate Off‐Target Effects

et al. 2020

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Life sciences have been revolutionized by genome editing (GE) tools, including zinc finger nucleases, transcription activator‐Like effector nucleases, and CRISPR (clustered regulatory interspaced short palindromic repeats)/Cas (CRISPR‐associated) systems, which make the targeted modification of genomic DNA of all organisms possible. CRISPR/Cas systems are being widely used because of their accuracy, efficiency, and cost‐effectiveness. Various classes of CRISPR/Cas systems have been developed, but their extensive use may be hindered by off‐target effects. Efforts are being made to reduce the off‐target effects of CRISPR/Cas9 by generating various CRISPR/Cas systems with high fidelity and accuracy. Several approaches have been applied to detect and evaluate the off‐target effects. Here, the current GE tools, the off‐target effects generated by GE technology, types of off‐target effects, mechanisms of off‐target effects, major concerns, and outcomes of off‐target effects in plants and animals are summarized. The methods to detect off‐target effects, tools for single‐guide RNA (sgRNA) design, evaluation and prediction of off‐target effects, and strategies to increase the on‐target efficiency and mitigate the off‐target impact on intended genome‐editing outcomes are summarized.

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“…For HTLV-1, the potential implication of the APOBEC3 subfamily (APOBEC3A to H) is one of the most well documented. The APOBEC3 subfamily is an ensemble of dC->U editing enzymes that can induce the conversion of cytosine to uracil by incorporating a G-to-A mutation in the retroviral genome resulting in premature stop codons [20,21]. It was first hypothesized that similarly to HIV-1, APOBEC3G (h3AG) could be packaged into HTLV-1 virions.…”

Section: Apobec Familymentioning

confidence: 99%

An Antiviral Process Targeting HTLV-1: The Complex Relationship between HTLV-1 and Nonsense-mediated mRNA Decay

Prochasson¹,

Jalinot²,

Mocquet³

2020

Preprint

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Before the adaptive immune response is established, retroviruses can be targeted by several cellular host factors at different stages of the viral replication cycle. This intrinsic immunity relies on a large diversity of antiviral processes. In the case of HTLV-1 infection, these active innate host defence mechanisms are debated. Among these mechanisms, we focused on a RNA decay pathway called nonsense-mediated mRNA decay (NMD), which can target multiple viral RNAs, including HTLV-1 unspliced RNA, as it has been recently demonstrated. NMD is a cotranslational process that depends on the RNA helicase UPF1 and regulates the expression of multiple types of host mRNAs. RNA sensitivity to NMD depends on mRNA organization and the ribonucleoprotein (mRNP) composition.HTLV-1 has evolved several means to evade the NMD threat, leading to NMD inhibition. In the early steps of infection, NMD inhibition favours the production of HTLV-1 infectious particles, which may contribute to the survival of the most fit clones despite genome instability; however, its direct longterm impact remains to be investigated.

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APOBEC: From mutator to editor

Cited by 54 publications

References 206 publications

APOBEC3B Activity Is Prevalent in Urothelial Carcinoma Cells and Only Slightly Affected by LINE-1 Expression

APOBEC3B Activity Is Prevalent in Urothelial Carcinoma Cells and Only Slightly Affected by LINE-1 Expression

CRISPR/Cas Systems in Genome Editing: Methodologies and Tools for sgRNA Design, Off‐Target Evaluation, and Strategies to Mitigate Off‐Target Effects

An Antiviral Process Targeting HTLV-1: The Complex Relationship between HTLV-1 and Nonsense-mediated mRNA Decay

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