Comprehensive analysis of differences of N
            <sup>6</sup>
            -methyladenosine RNA methylomes between high-fat-fed and normal mouse livers

Luo, Zupeng; Zhang, Zhiwang; Tai, Lina; Zhang, Lifang; Sun, Zheng; Zhou, Lei

doi:10.2217/epi-2019-0009

Cited by 67 publications

(52 citation statements)

References 56 publications

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“…Next, we further analyzed the distribution of ac 4 C peaks per gene between the two groups. Intriguingly, in the SLE and HC groups, the majority of ac 4 C-modified transcripts were observed to have one or two ac 4 C peak(s) per gene (77.06 and 86.53%, respectively), while a very small number of transcripts contained three or more ac 4 C peaks ( Figure 2C), which is similar to the trend of m 6 A characteristics previously reported in abnormal mouse livers (Luo et al, 2019). Furthermore, the proportion of ac 4 C-modified transcripts harboring only one ac 4 C peak was lower in CD4 + T cells of SLE groups (63.87% vs. 53.03%) than in HCs; whereas, the percentage of transcripts harboring two or more ac 4 C peaks was higher.…”

Section: Transcriptome-wide Global Ac 4 C Modification In Sle Patientsupporting

confidence: 87%

Epitranscriptomic N4-Acetylcytidine Profiling in CD4+ T Cells of Systemic Lupus Erythematosus

Guo

Shi

Wang

et al. 2020

Front. Cell Dev. Biol.

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The emerging epitranscriptome plays an essential role in autoimmune disease. As a novel mRNA modification, N4-acetylcytidine (ac 4 C) could promote mRNA stability and translational efficiency. However, whether epigenetic mechanisms of RNA ac 4 C modification are involved in systemic lupus erythematosus (SLE) remains unclear. Herein, we detected eleven modifications in CD4 + T cells of SLE patients using mass spectrometry (LC-MS/MS). Furthermore, using samples from four CD4 + T cell pools, we identified lower modification of ac 4 C mRNA in SLE patients as compared to that in healthy controls (HCs). Meanwhile, significantly lower mRNA acetyltransferase NAT10 expression was detected in lupus CD4 + T cells by RT-qPCR. We then illustrated the transcriptome-wide ac 4 C profile in CD4 + T cells of SLE patients by ac 4 C-RIP-Seq and found ac 4 C distribution in mRNA transcripts to be highly conserved and enriched in mRNA coding sequence regions. Using bioinformatics analysis, the 3879 and 4073 ac 4 C hyper-acetylated and hypoacetylated peaks found in SLE samples, respectively, were found to be significantly involved in SLE-related function enrichments, including multiple metabolic and transcription-related processes, ROSinduced cellular signaling, apoptosis signaling, and NF-κB signaling. Moreover, we demonstrated the ac 4 C-modified regulatory network of gene biological functions in lupus CD4 + T cells. Notably, we determined that the 26 upregulated genes with hyperacetylation played essential roles in autoimmune diseases and disease-related processes. Additionally, the unique ac 4 C-related transcripts, including USP18, GPX1, and RGL1, regulate mRNA catabolic processes and translational initiation. Our study identified novel dysregulated ac 4 C mRNAs associated with critical immune and inflammatory responses, that have translational potential in lupus CD4 + T cells. Hence, our findings reveal transcriptional significance and potential therapeutic targets of mRNA ac 4 C modifications in SLE pathogenesis.

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Section: Transcriptome-wide Global Ac 4 C Modification In Sle Patientsupporting

confidence: 87%

Epitranscriptomic N4-Acetylcytidine Profiling in CD4+ T Cells of Systemic Lupus Erythematosus

Guo

Shi

Wang

et al. 2020

Front. Cell Dev. Biol.

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“…Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was performed based on a previously reported procedure [32]. Total RNA was lysed into 100 base pair fragments using a GenSeqTM m5C RNA IP Kit (GenSeq Inc, China), and m5C immunoprecipitation was performed followed by RNA-seq library generation using a NEBNext ® Ultra II Directional RNA Library Prep Kit (New England Biolabs, Inc, USA).…”

Section: Library Construction and Sequencingmentioning

confidence: 99%

Overview of distinct 5-methylcytosine profiles of messenger RNA in human hepatocellular carcinoma and paired adjacent non-tumor tissues

Zhang

Zheng

et al. 2020

J Transl Med

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Background: Post-transcriptional methylation modifications, including 5-methylcytosine (m5C) modification, are closely related to the tumorigenesis of cancers. However, the mRNA profile of m5C modification in hepatocellular carcinoma (HCC) is unknown. Methods: Methylated RNA immunoprecipitation sequencing was performed to identify m5C peaks on mRNA of human HCC tissues and adjacent tissues, and differences in m5C between the two groups were analyzed. In addition, we conducted a bioinformatics analysis to predict the function of specific methylated transcripts. Results: We found that there was a noticeable difference in m5C between HCC and paired non-tumor tissues, suggesting that m5C could play a role in the pathogenesis of HCC. In addition, analyses of gene ontology and the Kyoto Encyclopedia of Genes and Genomes showed that the unique distribution pattern of mRNA m5C in HCC was associated with a wide range of cellular functions. Conclusions: Our results revealed different distribution patterns of m5C in HCC and adjacent tissues and provided new insights into a novel function of m5C RNA methylation of mRNA in HCC progression.

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“…The pathological character of NAFLD is caused by metabolic dysregulation of de novo lipogenesis, fatty acid uptake, fatty acid oxidation, and triglycerides export [97,98]. Previous studies have found that m 6 A alteration is highly related to the development of NAFLD [34,99,100]. The level of FTO is elevated in hepatic tissue at NAFLD patients with hyperglycemic and hyper-insulinemic [34], which can down-regulate mitochondrial content and upregulate triglyceride (TG) deposition, while FTO (R316A) mutant lacking demethylation activity and could not regulate mitochondria and TG content.…”

Section: A Methylation and Nafldmentioning

confidence: 99%

RNA N6-methyladenosine: a promising molecular target in metabolic diseases

Wang

Huang

et al. 2020

Cell Biosci

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N6-methyladenosine is a prevalent and abundant transcriptome modification, and its methylation regulates the various aspects of RNAs, including transcription, translation, processing and metabolism. The methylation of N6-methyladenosine is highly associated with numerous cellular processes, which plays important roles in the development of physiological process and diseases. The high prevalence of metabolic diseases poses a serious threat to human health, but its pathological mechanisms remain poorly understood. Recent studies have reported that the progression of metabolic diseases is closely related to the expression of RNA N6-methyladenosine modification. In this review, we aim to summarize the biological and clinical significance of RNA N6-methyladenosine modification in metabolic diseases, including obesity, type 2 diabetes, non-alcoholic fatty liver disease, hypertension, cardiovascular diseases, osteoporosis and immune-related metabolic diseases.

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Comprehensive analysis of differences of N ⁶ -methyladenosine RNA methylomes between high-fat-fed and normal mouse livers

Cited by 67 publications

References 56 publications

Epitranscriptomic N4-Acetylcytidine Profiling in CD4+ T Cells of Systemic Lupus Erythematosus

Epitranscriptomic N4-Acetylcytidine Profiling in CD4+ T Cells of Systemic Lupus Erythematosus

Overview of distinct 5-methylcytosine profiles of messenger RNA in human hepatocellular carcinoma and paired adjacent non-tumor tissues

RNA N6-methyladenosine: a promising molecular target in metabolic diseases

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Comprehensive analysis of differences of N 6 -methyladenosine RNA methylomes between high-fat-fed and normal mouse livers

Cited by 67 publications

References 56 publications

Epitranscriptomic N4-Acetylcytidine Profiling in CD4+ T Cells of Systemic Lupus Erythematosus

Epitranscriptomic N4-Acetylcytidine Profiling in CD4+ T Cells of Systemic Lupus Erythematosus

Overview of distinct 5-methylcytosine profiles of messenger RNA in human hepatocellular carcinoma and paired adjacent non-tumor tissues

RNA N6-methyladenosine: a promising molecular target in metabolic diseases

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Comprehensive analysis of differences of N ⁶ -methyladenosine RNA methylomes between high-fat-fed and normal mouse livers