Oxidative stress: One potential factor for arsenite-induced increase of N6-methyladenosine in human keratinocytes

Zhao, Tianhe; Li, Xinyang; Sun, Donglei; Zhang, Zunzhen

doi:10.1016/j.etap.2019.04.005

Cited by 54 publications

(26 citation statements)

References 43 publications

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“…Indeed, METTL3 is involved in different biological processes besides catalyzing m 6 A methylation (Zheng et al, 2019). Studies from our lab (H. Chen et al, 2019; Zhao et al, 2019, 2020) and other groups (Song & Feng, 2019; Zhang et al, 2019) have reported that changes in FTO and METTL3 expression are not always consistent with the alteration of m 6 A level. These findings collectively indicated that m 6 A methylation is a very dynamic modification in RNA due to diverse regulators.…”

Section: Discussionmentioning

confidence: 77%

“…This is because the expression of FTO is not associated with METTL3 (Tian et al, 2019;Zhou et al, 2019). Indeed, METTL3 is involved in different biological processes besides catalyzing m 6 A methylation (Zheng et al, 2019 Zhao et al, 2019Zhao et al, , 2020 and other groups (Song & Feng, 2019;Zhang et al, 2019) have reported that changes in FTO and METTL3 expression are not always consistent with the alteration of m 6 A level.…”

Section: Discussionmentioning

confidence: 98%

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Fat mass and obesity‐associated protein regulates lipogenesis via m⁶A modification in fatty acid synthase mRNA

Sun

Zhao

Zhang

et al. 2020

Cell Biology International

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As the first identified N6‐methyladenosine (m6A) demethylase, fat mass and obesity‐associated (FTO) protein is associated with fatty acid synthase (FASN) and lipid accumulation. However, little is known about the regulatory role of FTO in the expression of FASN and de novo lipogenesis through m6A modification. In this study, we used FTO small interfering RNA to explore the effects of FTO knockdown on hepatic lipogenesis and its underlying epigenetic mechanism in HepG2 cells. We found that knockdown of FTO increased m6A levels in total RNA and enhanced the expression of YTH domain family member 2 which serves as the m6A‐binding protein. The de novo lipogenic enzymes and intracellular lipid content were significantly decreased under FTO knockdown. Mechanistically, knockdown of FTO dramatically enhanced m6A levels in FASN messenger RNA (mRNA), leading to the reduced expression of FASN mRNA through m6A‐mediated mRNA decay. The protein expressions of FASN along with acetyl CoA carboxylase and ATP‐citrate lyase were further decreased, which inhibited de novo lipogenesis, thereby resulting in the deficiency of lipid accumulation in HepG2 cells and the induction of cellular apoptosis. The results reveal that FTO regulates hepatic lipogenesis via FTO‐dependent m6A demethylation in FASN mRNA and indicate the critical role of FTO‐mediated lipid metabolism in the survival of HepG2 cells. This study provides novel insights into a unique RNA epigenetic mechanism by which FTO mediates hepatic lipid accumulation through m6A modification and indicates that FTO could be a potential target for obesity‐related diseases and cancer.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 98%

Fat mass and obesity‐associated protein regulates lipogenesis via m⁶A modification in fatty acid synthase mRNA

Sun

Zhao

Zhang

et al. 2020

Cell Biology International

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“…In human keratinocytes, ROS was induced by arsenite, an environmental carcinogen, resulting in increased expression of WTAP and METTL14 and overall m 6 A levels [22,61]. Specific m 6 A increases were also identified on cell surface receptor SLC22A17, potassium channel KCNQ5, ATP binding cassette subfamily A member 5 (ABCA5) and HECT domain E3 Ubiquitin Protein Ligase 4 (HECTD4), leading to decreased mRNA expression of these genes [22] ( Figures 2C and 3A, Table 1). Further studies are needed to elucidate the functional significance of these targets in this context.…”

Section: Writersmentioning

confidence: 98%

“…These results suggest that loss of NSUN2 may be necessary to induce the cellular stress response [23] ( Figures 2B and 3A, Table 1). In human keratinocytes, ROS was induced by arsenite, an environmental carcinogen, resulting in increased expression of WTAP and METTL14 and overall m 6 A levels [22,61]. Furthermore, m 5 C writers have also been implicated in the oxidative stress response.…”

Section: Writersmentioning

confidence: 99%

Context-Dependent Roles of RNA Modifications in Stress Responses and Diseases

Wilkinson

Cui

2021

IJMS

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RNA modifications are diverse post-transcriptional modifications that regulate RNA metabolism and gene expression. RNA modifications, and the writers, erasers, and readers that catalyze these modifications, serve as important signaling machineries in cellular stress responses and disease pathogenesis. In response to stress, RNA modifications are mobilized to activate or inhibit the signaling pathways that combat stresses, including oxidative stress, hypoxia, therapeutic stress, metabolic stress, heat shock, DNA damage, and ER stress. The role of RNA modifications in response to these cellular stressors is context- and cell-type-dependent. Due to their pervasive roles in cell biology, RNA modifications have been implicated in the pathogenesis of different diseases, including cancer, neurologic and developmental disorders and diseases, and metabolic diseases. In this review, we aim to summarize the roles of RNA modifications in molecular and cellular stress responses and diseases.

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“…However, there is very limited information about the impact of environmental chemicals on m6A methylation patterns and the associated functional consequences on gene expression patterns. Recent studies have demonstrated that environmental chemicals such as arsenite affect RNA methylase and demethylase protein expression (Bai et al 2018;Cayir et al 2019;Chen et al 2019;Gu et al 2018;Zhao et al 2019). These studies have also measured global m6A RNA content using an ELISA-based method.…”

Section: Introductionmentioning

confidence: 99%

PCB126 exposure revealed alterations in m6A RNA modifications in transcripts associated with AHR activation

Aluru

Karchner

2020

Preprint

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AbstractChemical modifications of proteins, DNA and RNA moieties play critical roles in regulating gene expression. Emerging evidence suggests these RNA modifications (epitranscriptomics) have substantive roles in basic biological processes. One of the most common modifications in mRNA and noncoding RNAs is N6-methyladenosine (m6A). In a subset of mRNAs, m6A sites are preferentially enriched near stop codons, in 3’ UTRs, and within exons, suggesting an important role in the regulation of mRNA processing and function including alternative splicing and gene expression. Very little is known about the effect of environmental chemical exposure on m6A modifications. As many of the commonly occurring environmental contaminants alter gene expression profiles and have detrimental effects on physiological processes, it is important to understand the effects of exposure on this important layer of gene regulation. Hence, the objective of this study was to characterize the acute effects of developmental exposure to PCB126, an environmentally relevant dioxin-like PCB, on m6A methylation patterns. We exposed zebrafish embryos to PCB126 for 6 hours starting from 72 hours post-fertilization and profiled m6A RNA using methylated RNA immunoprecipitation followed by sequencing (MeRIP-seq). Our analysis revealed 117 and 217 m6A peaks in the DMSO and PCB126 samples (FDR 5%), respectively. The majority of the peaks were preferentially located around the 3’UTR and stop codons. Statistical analysis revealed 15 m6A marked transcripts to be differentially methylated by PCB126 exposure. These include transcripts that are known to be activated by AHR agonists (e.g., ahrra, tiparp, nfe2l2b) as well as others that are important for normal development (vgf, cebpd, foxi1). These results suggest that environmental chemicals such as dioxin-like PCBs could affect developmental gene expression patterns by altering m6A levels. Further studies are necessary to understand the functional consequences of exposure-associated alterations in m6A levels.

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Oxidative stress: One potential factor for arsenite-induced increase of N6-methyladenosine in human keratinocytes

Cited by 54 publications

References 43 publications

Fat mass and obesity‐associated protein regulates lipogenesis via m⁶A modification in fatty acid synthase mRNA

Fat mass and obesity‐associated protein regulates lipogenesis via m⁶A modification in fatty acid synthase mRNA

Context-Dependent Roles of RNA Modifications in Stress Responses and Diseases

PCB126 exposure revealed alterations in m6A RNA modifications in transcripts associated with AHR activation

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Oxidative stress: One potential factor for arsenite-induced increase of N6-methyladenosine in human keratinocytes

Cited by 54 publications

References 43 publications

Fat mass and obesity‐associated protein regulates lipogenesis via m6A modification in fatty acid synthase mRNA

Fat mass and obesity‐associated protein regulates lipogenesis via m6A modification in fatty acid synthase mRNA

Context-Dependent Roles of RNA Modifications in Stress Responses and Diseases

PCB126 exposure revealed alterations in m6A RNA modifications in transcripts associated with AHR activation

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Fat mass and obesity‐associated protein regulates lipogenesis via m⁶A modification in fatty acid synthase mRNA

Fat mass and obesity‐associated protein regulates lipogenesis via m⁶A modification in fatty acid synthase mRNA