RNA Epigenetics: RNA Modification and Epitranscriptome Analysis

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Technologies and Resources for Genetics".

Deadline for manuscript submissions: closed (15 April 2023) | Viewed by 15933

Special Issue Editors

The Department of Biological Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, China
Interests: epitranscriptomics & RNA epigenetics; bioinformatics; machine learning and pattern recognition; precision medicine & personalized medicine
Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350004, China
Interests: epitranscriptomics; bioinformatics; cancer biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We would like to invite you to participate in this Special Issue, entitled RNA Epigenetics: RNA Modification and Epitranscriptome Analysis.

With the recent advances in the exploration of RNA epigenetics, more than 150 types of RNA modifications have been identified, covering all three domains (bacteria, archaea and eukarya). These specific chemical modifications of biological molecules are an efficient way to regulate molecular functions and biological processes. Recent studies have proven that RNA modifications are critical to development, including embryo development and stem cell fate determination. In addition, RNA modification pathways are found to be dysregulated in multiple human diseases.

In this Special Issue, we aim to gather articles from epi-transcriptomics studies on every aspect of RNA epigenetics to decipher the regulation and function of RNA epigenetics on any form of life. We will consider studies on topics including, but not limited to new experimental results, interesting discoveries, new biomolecular mechanisms, novel computational/experimental approaches, bioinformatics and epigenetics analyses, new software tools for the analysis of epigenetics data, RNA modifications databases, as well as review articles related to post-transcriptional RNA modification and epitranscriptome for publication.

However, simple biomarker (or signature) prediction and analysis based on mining public biological databases such as TCGA or ENCODE without in-depth experimental validation will NOT be considered.

Dr. Jia Meng
Dr. Kunqi Chen
Guest Editors

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Keywords

  • epitranscriptome
  • RNA modification
  • RNA epigenetics
  • RNA editing
  • diseases
  • bioinformatics
  • machine learning

Published Papers (7 papers)

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Research

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15 pages, 3496 KiB  
Article
Modification and Expression of mRNA m6A in the Lateral Habenular of Rats after Long-Term Exposure to Blue Light during the Sleep Period
by Yinhan Li, Jinjin Ren, Zhaoting Zhang, Yali Weng, Jian Zhang, Xinhui Zou, Siying Wu and Hong Hu
Genes 2023, 14(1), 143; https://0-doi-org.brum.beds.ac.uk/10.3390/genes14010143 - 04 Jan 2023
Cited by 2 | Viewed by 2389
Abstract
Artificial lighting, especially blue light, is becoming a public-health risk. Excessive exposure to blue light at night has been reported to be associated with brain diseases. However, the mechanisms underlying neuropathy induced by blue light remain unclear. An early anatomical tracing study described [...] Read more.
Artificial lighting, especially blue light, is becoming a public-health risk. Excessive exposure to blue light at night has been reported to be associated with brain diseases. However, the mechanisms underlying neuropathy induced by blue light remain unclear. An early anatomical tracing study described the projection of the retina to the lateral habenula (LHb), whereas more mechanistic reports are available on multiple brain functions and neuropsychiatric disorders in the LHb, which are rarely seen in epigenetic studies, particularly N6-methyladenosine (m6A). The purpose of our study was to first expose Sprague-Dawley rats to blue light (6.11 ± 0.05 mW/cm2, the same irradiance as 200 lx of white light in the control group) for 4 h, and simultaneously provide white light to the control group for the same time to enter a sleep period. The experiment was conducted over 12 weeks. RNA m6A modifications and different mRNA transcriptome profiles were observed in the LHb. We refer to this experimental group as BLS. High-throughput MeRIP-seq and mRNA-seq were performed, and we used bioinformatics to analyze the data. There were 188 genes in the LHb that overlapped between differentially m6A-modified mRNA and differentially expressed mRNA. The Kyoto Encyclopedia of Genes and Genomes and gene ontology analysis were used to enrich neuroactive ligand–receptor interaction, long-term depression, the cyclic guanosine monophosphate-dependent protein kinase G (cGMP-PKG) signaling pathway, and circadian entrainment. The m6A methylation level of the target genes in the BLS group was disordered. In conclusion, this study suggests that the mRNA expression and their m6A of the LHb were abnormal after blue light exposure during the sleep period, and the methylation levels of target genes related to synaptic plasticity were disturbed. This study offers a theoretical basis for the scientific use of light. Full article
(This article belongs to the Special Issue RNA Epigenetics: RNA Modification and Epitranscriptome Analysis)
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16 pages, 5517 KiB  
Article
Integrated Profiles of Transcriptome and mRNA m6A Modification Reveal the Intestinal Cytotoxicity of Aflatoxin B1 on HCT116 Cells
by Yajiao Wu, Wenqiang Bao, Jinjin Ren, Chutao Li, Mengting Chen, Dongcheng Zhang and An Zhu
Genes 2023, 14(1), 79; https://0-doi-org.brum.beds.ac.uk/10.3390/genes14010079 - 27 Dec 2022
Cited by 3 | Viewed by 2031
Abstract
Aflatoxin B1 (AFB1) is widely prevalent in foods and animal feeds and is one of the most toxic and carcinogenic aflatoxin subtypes. Existing studies have proved that the intestine is targeted by AFB1, and adverse organic effects have been observed. This study aimed [...] Read more.
Aflatoxin B1 (AFB1) is widely prevalent in foods and animal feeds and is one of the most toxic and carcinogenic aflatoxin subtypes. Existing studies have proved that the intestine is targeted by AFB1, and adverse organic effects have been observed. This study aimed to investigate the relationship between AFB1-induced intestinal toxicity and N6-methyladenosine (m6A) RNA methylation, which involves the post-transcriptional regulation of mRNA expression. The transcriptome-wide m6A methylome and transcriptome profiles in human intestinal cells treated with AFB1 are presented. Methylated RNA immunoprecipitation sequencing and mRNA sequencing were carried out to determine the distinctions in m6A methylation and different genes expressed in AFB1-induced intestinal toxicity. The results showed that there were 2289 overlapping genes of the differentially expressed mRNAs and differentially m6A-methylation-modified mRNAs. After enrichment of the signaling pathways and biological processes, these genes participated in the terms of the cell cycle, endoplasmic reticulum, tight junction, and mitophagy. In conclusion, the study demonstrated that AFB1-induced HCT116 injury was related to the disruptions to the levels of m6A methylation modifications of target genes and the abnormal expression of m6A regulators. Full article
(This article belongs to the Special Issue RNA Epigenetics: RNA Modification and Epitranscriptome Analysis)
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12 pages, 2610 KiB  
Article
Integrative Transcriptomic Analysis Identify Potential m6A Pathway-Related Drugs That Inhibit Cancer Cell Proliferation
by Jingkun Yi, Rucong Liu, Yu Liu, Ting Guo, Yang Li and Yuan Zhou
Genes 2022, 13(11), 2011; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13112011 - 02 Nov 2022
Cited by 1 | Viewed by 1461
Abstract
Recent studies have found that m6A modification of mRNA may play important roles in the progression of various types of cancers. However, current knowledge about drugs that can interfere with m6A methylation and inhibit cancer cell proliferation is still far from comprehensive. To [...] Read more.
Recent studies have found that m6A modification of mRNA may play important roles in the progression of various types of cancers. However, current knowledge about drugs that can interfere with m6A methylation and inhibit cancer cell proliferation is still far from comprehensive. To this end, we performed integrative analysis on transcriptome data with perturbation of m6A writers or erasers and identified consensus m6A-related differentially expressed genes (DEGs). Comparative analysis of these m6A-related DEGs with Connectivity Map signatures highlight potential m6A-targeted drugs. Among them, we experimentally verified the inhibitory effects of AZ628 on the proliferation of human breast cancer cell lines and R428 on the proliferation of human melanoma cell lines. Both drugs can significantly reduce the cellular level of m6A modification. These results suggest an m6A-related new target pathway by AZ628 and R428 and provide new candidate m6A-related drugs that inhibit cancer cell proliferation. Full article
(This article belongs to the Special Issue RNA Epigenetics: RNA Modification and Epitranscriptome Analysis)
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11 pages, 1959 KiB  
Article
RNA m6A Modification Changes in Postmortem Nucleus Accumbens of Subjects with Alcohol Use Disorder: A Pilot Study
by Ying Liu and Huiping Zhang
Genes 2022, 13(6), 958; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13060958 - 27 May 2022
Cited by 10 | Viewed by 1992
Abstract
Background: The nucleus accumbens (NAc) is a key brain structure mediating the rewarding effect of alcohol and drug abuse. Chronic alcohol consumption may alter RNA methylome (or epitranscriptome) in the NAc, leading to altered gene expression and thus behavioral neuroadaptation to alcohol. Methods: [...] Read more.
Background: The nucleus accumbens (NAc) is a key brain structure mediating the rewarding effect of alcohol and drug abuse. Chronic alcohol consumption may alter RNA methylome (or epitranscriptome) in the NAc, leading to altered gene expression and thus behavioral neuroadaptation to alcohol. Methods: This pilot study profiled the epitranscriptomes of mRNAs, long noncoding RNAs (lncRNAs), and microRNAs (miRNAs) in postmortem NAc of three male Caucasian subjects with alcohol use disorder (AUD) and three matched male Caucasian control subjects using Arraystar’s m6A-mRNA&lncRNA Epitranscriptomic Microarray assay. Differentially methylated (DM) RNAs and the function of DM RNAs were analyzed by biostatistics and bioinformatics programs. Results: 26 mRNAs were hypermethylated and three mRNAs were hypomethylated in the NAc of AUD subjects (≥2-fold changes and p ≤ 0.05). Most of these 29 DM mRNAs are involved in immune-related pathways (e.g., IL-17 signaling). Moreover, four lncRNAs were hypermethylated and one lncRNA was hypomethylated in the NAc of AUD subjects (≥2-fold changes and p ≤ 0.05). Additionally, three miRNAs were hypermethylated in the NAc of AUD subjects (≥2-fold changes and p ≤ 0.05). Conclusions: This study revealed RNA methylomic changes in the NAc of AUD subjects, suggesting that chronic alcohol consumption may lead to AUD through epitranscriptomic RNA modifications. Our findings need to be replicated in a larger sample. Full article
(This article belongs to the Special Issue RNA Epigenetics: RNA Modification and Epitranscriptome Analysis)
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17 pages, 3812 KiB  
Article
Effect of Humantenine on mRNA m6A Modification and Expression in Human Colon Cancer Cell Line HCT116
by Yajiao Wu, Xiaoying Chen, Wenqiang Bao, Xinyu Hong, Chutao Li, Jiatong Lu, Dongcheng Zhang and An Zhu
Genes 2022, 13(5), 781; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13050781 - 27 Apr 2022
Cited by 9 | Viewed by 2378
Abstract
Humantenine, an alkaloid isolated from the medicinal herb Gelsemium elegans (Gardner & Chapm.) Benth., has been reported to induce intestinal irritation, but the underlying toxicological mechanisms remain unclear. The object of the present study was to investigate the RNA N6-methyladenosine (m6A) modification and [...] Read more.
Humantenine, an alkaloid isolated from the medicinal herb Gelsemium elegans (Gardner & Chapm.) Benth., has been reported to induce intestinal irritation, but the underlying toxicological mechanisms remain unclear. The object of the present study was to investigate the RNA N6-methyladenosine (m6A) modification and distinct mRNA transcriptome profiles in humantenine-treated HCT116 human colon cancer cells. High-throughput MeRIP-seq and mRNA-seq were performed, and bioinformatic analysis was performed to reveal the role of abnormal RNA m6A modification and mRNA expression in humantenine-induced intestinal cell toxicity. After humantenine treatment of HCT116 cells, 1401 genes were in the overlap of differentially m6A-modified mRNA and differentially expressed mRNA. The Kyoto Encyclopedia of Genes and Genomes and Gene Ontology annotation terms for actin cytoskeleton, tight junctions, and adherens junctions were enriched. A total of 11 kinds of RNA m6A methylation regulators were differentially expressed. The m6A methylation levels of target genes were disordered in the humantenine group. In conclusion, this study suggested that the HCT116 cell injury induced by humantenine was associated with the abnormal mRNA expression of m6A regulators, as well as disordered m6A methylation levels of target genes. Full article
(This article belongs to the Special Issue RNA Epigenetics: RNA Modification and Epitranscriptome Analysis)
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13 pages, 1019 KiB  
Article
m5CRegpred: Epitranscriptome Target Prediction of 5-Methylcytosine (m5C) Regulators Based on Sequencing Features
by Zhizhou He, Jing Xu, Haoran Shi and Shuxiang Wu
Genes 2022, 13(4), 677; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13040677 - 12 Apr 2022
Cited by 10 | Viewed by 2546
Abstract
5-methylcytosine (m5C) is a common post-transcriptional modification observed in a variety of RNAs. m5C has been demonstrated to be important in a variety of biological processes, including RNA structural stability and metabolism. Driven by the importance of m5C modification, many projects focused on [...] Read more.
5-methylcytosine (m5C) is a common post-transcriptional modification observed in a variety of RNAs. m5C has been demonstrated to be important in a variety of biological processes, including RNA structural stability and metabolism. Driven by the importance of m5C modification, many projects focused on the m5C sites prediction were reported before. To better understand the upstream and downstream regulation of m5C, we present a bioinformatics framework, m5CRegpred, to predict the substrate of m5C writer NSUN2 and m5C readers YBX1 and ALYREF for the first time. After features comparison, window lengths selection and algorism comparison on the mature mRNA model, our model achieved AUROC scores 0.869, 0.724 and 0.889 for NSUN2, YBX1 and ALYREF, respectively in an independent test. Our work suggests the substrate of m5C regulators can be distinguished and may help the research of m5C regulators in a special condition, such as substrates prediction of hyper- or hypo-expressed m5C regulators in human disease. Full article
(This article belongs to the Special Issue RNA Epigenetics: RNA Modification and Epitranscriptome Analysis)
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Review

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18 pages, 2140 KiB  
Review
RNA Epigenetics in Chronic Lung Diseases
by Xiaorui Wang, Zhihou Guo and Furong Yan
Genes 2022, 13(12), 2381; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13122381 - 16 Dec 2022
Cited by 3 | Viewed by 2183
Abstract
Chronic lung diseases are highly prevalent worldwide and cause significant mortality. Lung cancer is the end stage of many chronic lung diseases. RNA epigenetics can dynamically modulate gene expression and decide cell fate. Recently, studies have confirmed that RNA epigenetics plays a crucial [...] Read more.
Chronic lung diseases are highly prevalent worldwide and cause significant mortality. Lung cancer is the end stage of many chronic lung diseases. RNA epigenetics can dynamically modulate gene expression and decide cell fate. Recently, studies have confirmed that RNA epigenetics plays a crucial role in the developing of chronic lung diseases. Further exploration of the underlying mechanisms of RNA epigenetics in chronic lung diseases, including lung cancer, may lead to a better understanding of the diseases and promote the development of new biomarkers and therapeutic strategies. This article reviews basic information on RNA modifications, including N6 methylation of adenosine (m6A), N1 methylation of adenosine (m1A), N7-methylguanosine (m7G), 5-methylcytosine (m5C), 2′O-methylation (2′-O-Me or Nm), pseudouridine (5-ribosyl uracil or Ψ), and adenosine to inosine RNA editing (A-to-I editing). We then show how they relate to different types of lung disease. This paper hopes to summarize the mechanisms of RNA modification in chronic lung disease and finds a new way to develop early diagnosis and treatment of chronic lung disease. Full article
(This article belongs to the Special Issue RNA Epigenetics: RNA Modification and Epitranscriptome Analysis)
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