Article
Biotechnology & Applied Microbiology
Zachary Johnson, Yu Lin, Hehuang Xie, Xiguang Xu
Summary: Post-transcriptional RNA modifications play a crucial role in neuronal differentiation and synapse development in the mammalian brain. In this study, the researchers characterized the methylation profiles of mRNA in the developing brain, identifying m5C sites that are consistently methylated across different conditions. They found that the majority of these methylated sites are hypermethylated in neurons compared to NSCs, and are associated with genes involved in positive transcriptional regulation and axon extension. Furthermore, there were significant changes in RNA cytosine methylation and the expression of related genes during early postnatal brain development, with differentially methylated transcripts enriched for genes regulating synaptic plasticity.
Article
Biochemistry & Molecular Biology
Guangying Luo, Weiwei Xu, Xiaoyan Chen, Siqi Wang, Jiao Wang, Feng Dong, Dan-Ning Hu, Peter S. Reinach, Dongsheng Yan
Summary: This study reveals the biological roles and regulatory mechanisms of RNA m(5)C in uveal melanoma. NSUN2-mediated m(5)C modification regulates cell migration and proliferation by targeting beta-Catenin, providing potential therapeutic targets for the management of UM pathogenesis.
Article
Cell Biology
Yuanbo Hu, Chenbin Chen, Xinya Tong, Sian Chen, Xianjing Hu, Bujian Pan, Xiangwei Sun, Zhiyuan Chen, Xinyu Shi, Yingying Hu, Xian Shen, Xiangyang Xue, Mingdong Lu
Summary: NSUN2, a m5C RNA methyltransferase, is upregulated in gastric cancer (GC) and predicts poor prognosis. It promotes cell proliferation, migration, and invasion, possibly through direct interaction with SUMO-2/3 for nuclear transport. NSUN2 is involved in multiple cancer-related signaling pathways, with potential target genes such as PIK3R1 and PCYT1A in GC progression.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Yueqin Wang, Jingyao Wei, Luyao Feng, Ouwen Li, Lan Huang, Shaoxuan Zhou, Yingjie Xu, Ke An, Yu Zhang, Ruiying Chen, Lulu He, Qiming Wang, Han Wang, Yue Du, Ruijuan Liu, Chunmin Huang, Xiaojian Zhang, Yun-gui Yang, Quancheng Kan, Xin Tian
Summary: The study found that RNA methylation modification m(5)C and NSUN2 are significantly correlated with drug resistance in EGFR-mutant non-small-cell lung cancer. Overexpression of NSUN2 leads to gefitinib resistance and tumor recurrence, while genetic inhibition of NSUN2 results in tumor regression and overcomes intrinsic resistance to gefitinib. The study also reveals that NSUN2 promotes the translation of QSOX1 gene through methylation, mediating intrinsic resistance to gefitinib in EGFR-mutant non-small-cell lung cancer.
Article
Ophthalmology
Guangying Luo, Weiwei Xu, Xiaoyan Chen, Wenji Xu, Shuai Yang, Jiao Wang, Yong Lin, Peter S. Reinach, Dongsheng Yan
Summary: This study investigates the role of NSUN2 in corneal epithelial wound healing (CEWH) and its underlying mechanisms. The expression of NSUN2 and RNA m5C level significantly increased during CEWH. NSUN2 knockdown delays CEWH and inhibits cell proliferation and migration, while NSUN2 overexpression enhances cell proliferation and migration. Mechanistically, NSUN2 increases the translation of UHRF1 mRNA through the binding of RNA m5C reader Aly/REF export factor, thereby modulating CEWH. This finding highlights the critical importance of this novel epitranscriptomic mechanism in controlling CEWH.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Review
Immunology
Xinyu Gu, Xiao Ma, Chao Chen, Jun Guan, Jing Wang, Shanshan Wu, Haihong Zhu
Summary: RNA modification plays a crucial role in epigenetics at the posttranscriptional level. The m(5)C modification of various types of RNA, such as mRNA, tRNA, rRNA, and lncRNA, affects gene expression, metabolism, and is associated with diseases including cancer. Additionally, m(5)C modifications impact the tumor microenvironment by influencing different immune cell populations and their function.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Meng Liu, Gangqiang Guo, Pengge Qian, Jianbing Mu, Binbin Lu, Xiaoqin He, Yanting Fan, Xiaomin Shang, Guang Yang, Shijun Shen, Wenju Liu, Liping Wang, Liang Gu, Quankai Mu, Xinyu Yu, Yuemeng Zhao, Richard Culleton, Jun Cao, Lubin Jiang, Thomas E. Wellems, Jing Yuan, Cizhong Jiang, Qingfeng Zhang
Summary: m5C modification is an important regulator of mRNA stability and translation efficiency in malaria parasites. This study characterized the landscape of m5C mRNA modifications in different developmental stages of rodent and human malaria parasites. The results showed that m5C modifications confer stability to Plasmodium transcripts and that NSUN2 is a major mRNA m5C methyltransferase in malaria parasites. Knockout of the nsun2 gene resulted in reduced m5C modification and impaired gametocyte production, which was rescued by restoration of the nsun2 gene. These findings highlight the significant role of NSUN2-mediated m5C modifications in mRNA transcript stability and sexual differentiation in malaria parasites.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Xiguang Xu, Zachary Johnson, Amanda Wang, Rachel L. Padget, James W. Smyth, Hehuang Xie
Summary: This study reports the transcriptome-wide influence of folate on mRNA m(5)C methylation and translation in neural stem cells (NSCs) and reveals a potential link between mRNA m(5)C methylation and mRNA translation.
Article
Oncology
Sipeng Zuo, Lin Li, Xuyang Wen, Xiang Gu, Ai Zhuang, Rui Li, Fuxiang Ye, Shengfang Ge, Xianqun Fan, Jiayan Fan, Peiwei Chai, Linna Lu
Summary: This study reveals that NSUN2-mediated m(5)C RNA methylation promotes purine biosynthesis in retinoblastoma (RB) progression. The downstream target of NSUN2, phosphoribosylformylglycinamidine synthase (PFAS), is identified through multiomics analyses. The m(5)C reader protein ALYREF recognizes the m(5)C modification on PFAS, enhancing its RNA stability and increasing its expression.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Qiaofeng Zhang, Furong Liu, Wei Chen, Hongrui Miao, Huifang Liang, Zhibin Liao, Zhanguo Zhang, Bixiang Zhang
Summary: Epigenetic modification is crucial in regulating biological processes in eukaryotic cells, particularly in tumor metastasis. Recent studies have focused on the characterization of RNA and DNA methylation, but the mechanisms of RNA m(5)C methylation in cell mobility and metastasis remain unclear.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Cell Biology
Zhidong Huang, Junfan Pan, Helin Wang, Xianqiang Du, Yusheng Xu, Zhitang Wang, Debo Chen
Summary: The study investigated the gene expression, clinicopathological characteristics, and prognostic value of m5C regulators in TNBC, revealing their potential as novel prognostic markers and their impact on tumor development and the tumor immune microenvironment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Lixiao Chen, Jian Ding, Baoxin Wang, Xinwei Chen, Xinjiang Ying, Ziwei Yu, Pin Dong
Summary: In hypopharyngeal squamous cell carcinoma (HPSCC), the RNA methyltransferase NSUN2 is highly expressed and its knockdown inhibits cell proliferation and invasion, potentially through upregulating TEAD1. This indicates that NSUN2 may serve as an oncogene and potential therapeutic target in HPSCC.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Cell Biology
Ying Li, Yiwen Xia, Tianlu Jiang, Zetian Chen, Yikai Shen, Jie Lin, Li Xie, Chao Gu, Jialun Lv, Chen Lu, Diancai Zhang, Hao Xu, Li Yang, Zekuan Xu, Linjun Wang
Summary: Neural invasion (NI) is a crucial pathological feature of gastric cancer (GC), associated with tumor recurrence and poor prognosis. This study revealed that DIAPH2-AS1, an upregulated long noncoding RNA (lncRNA) in NI-positive GC tissues, promoted migration, invasion, and NI potential of GC cells. Mechanistically, DIAPH2-AS1 interacted with NSUN2, stabilizing it from degradation and improving the stability of NTN1 mRNA via m5C modification. DIAPH2-AS1-NSUN2-NTN1 axis could serve as a potential therapeutic target for NI-positive GC.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Saima Usman, Ahmad Jamal, Antesar Bushaala, Naushin H. H. Waseem, Hebah Al-Dehlawi, William Andrew Yeudall, Muy-Teck Teh, Hemanth Tummala, Ahmad Waseem
Summary: In advanced metastatic cancers, the expression of vimentin is frequently observed and it is associated with reduced patient survival and poor prognosis. Vimentin can change the shape of breast cancer cells and increase cell migration by suppressing epithelial characteristics and affecting gene expression related to cell-cell adhesion. Additionally, the presence of vimentin can alter nuclear architecture and downregulate genes involved in cell-cell adhesion, leading to increased cell migration.
Article
Multidisciplinary Sciences
Richard C. Tyser, Elmir Mahammadov, Shota Nakanoh, Ludovic Vallier, Antonio Scialdone, Shankar Srinivas
Summary: The single-cell transcriptional profile of a human embryo between 16 and 19 days after fertilization shows similarities and differences in gastrulation compared to mouse and non-human primate models. This study provides new insights into human development and offers valuable information for directed differentiation of human cells in vitro.
