Article
Chemistry, Multidisciplinary
Yuru Wang, Zijie Zhang, Caraline Sepich-Poore, Lisheng Zhang, Yu Xiao, Chuan He
Summary: The study introduces a new method, LEAD-m(6)A-seq, which significantly improves the efficiency of locus-specific analysis of m(6)A modification by coupling it to next generation sequencing technology. This strategy allows for high-throughput validation and detection of m(6)A modification at selected sites, with high reproducibility in evaluating differential methylation levels.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Neurosciences
Qiang Wang, Yundan Liang, Xiaolei Luo, Yuqing Liu, Xiaoli Zhang, Linbo Gao
Summary: m6A modification, a reversible epigenetic modification occurring in RNA, is dynamically regulated by writers, erasers, and readers. With the strongest tissue specificity in brain tissue, m6A plays crucial roles in central nervous system (CNS) injuries by affecting various aspects of mRNA function. Understanding the dynamics, functions, and machinery of m6A modification presents an opportunity for designing novel therapeutic agents for CNS injuries.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Cell Biology
Fei Wang, Jun Zhang, Xianrong Lin, Lu Yang, Qi Zhou, Xue Mi, Qiujie Li, Shen Wang, Dawei Li, Xiao-Min Liu, Jun Zhou
Summary: METTL16 is found to have dual localization in the nucleus and cytoplasm. It interacts with eIF4E2 to inhibit its translation inhibitory function, promoting protein synthesis and suppressing lung tumorigenesis. This study reveals the role of METTL16 in translational regulation and provides a therapeutic target for lung cancer treatment.
Article
Biochemistry & Molecular Biology
Emily S. Talic, Ashley Wooten, Tonya N. Zeczycki, Kyle D. Mansfield
Summary: METTL16 is a human m6A RNA methyltransferase known for modifying U6 and MAT2A RNAs. It is unclear whether it modifies other RNAs and the importance of its different RNA-binding domains. By mutating specific domains of METTL16 protein, we observed changes in RNA-binding ability, cell processes, and proliferation.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yun-Zhang Dai, Yong-da Liu, Jie Li, Mei-Ting Chen, Mei Huang, Fang Wang, Qing-Song Yang, Ji-Hang Yuan, Shu-Han Sun
Summary: This study identified the METTL16/RAB11B-AS1 regulatory axis in HCC, which represented novel targets for HCC prognosis and treatment.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2022)
Review
Cardiac & Cardiovascular Systems
Ye-shi Chen, Xin-ping Ouyang, Xiao-hua Yu, Petr Novak, Le Zhou, Ping-ping He, Kai Yin
Summary: N6-methyladenosine (m(6)A) is the most abundant and prevalent epigenetic modification of mRNA in mammals, regulating the fate of target mRNAs by influencing splicing, translation, and decay. Its important role in cardiovascular diseases, such as cardiac remodeling, heart failure, atherosclerosis, and congenital heart disease, has been highlighted in recent studies, although the exact mechanisms are not fully elucidated.
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
(2021)
Review
Cell Biology
Kurtis Breger, Charlotte N. Kunkler, Nathan J. O'Leary, Jacob P. Hulewicz, Jessica A. Brown
Summary: Despite being discovered 75 years ago, the biological functions of modified nucleic acids are still being explored. N-6-methyladenosine (m(6)A) is the most abundant modification in eukaryotic mRNA and has also been found in non-coding RNAs. m(6)A marks can affect RNA structure and initiate specific RNA-protein interactions, leading to changes in splicing, mRNA turnover, and translation. Recent research has identified four human methyltransferases responsible for writing m(6)A marks, and their structures and functions have been studied. Understanding these methyltransferases is crucial for establishing the m(6)A epitranscriptome and expanding our knowledge of the RNA world.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2023)
Article
Multidisciplinary Sciences
Wei Hong, Yanding Zhao, Yi-Lan Weng, Chao Cheng
Summary: We developed a Random Forest model to analyze the interaction between RNA-binding proteins (RBPs) and N6-methyladenosine (m6A) modifications by integrating binding signals from hundreds of RBPs. Accurate prediction of m6A sites revealed significant connections between RBP bindings and m6A modifications. The relative importance of different RBPs provided a quantitative metric to evaluate their interactions with m6A modifications. Redundancy analysis showed similar binding patterns between several RBPs and m6A sites. The model exhibited high prediction accuracy in various cell lines, suggesting a conservative RBP interaction network in regulating m6A occupancy. Specific RBPs can bind to corresponding regional m6A sites and deploy distinct regulatory processes, such as cleavage site selection of alternative polyadenylation (APA). Additionally, the integration of histone modifications in the RF model identified H3K36me3 and H3K27me3 as determining features for m6A distribution.
Review
Medicine, Research & Experimental
Jingyuan Zhang, Tianming Qiu, Xiaofeng Yao, Xiance Sun
Summary: N6-methyladenosine (m6A) methylation modification is a prevalent epigenetic modification of eukaryotic RNA and is associated with various biological processes and disease states. Ferroptosis, a recently discovered regulatory cell death characterized by excessive lipid peroxidation, plays a significant role in the progression of diverse diseases. The key regulators of ferroptosis show abnormal m6A levels under different pathological conditions. However, the correlation between m6A-modified ferroptosis and multiple diseases is not well understood. This review summarizes the functions of m6A in ferroptosis and its association with the initiation and progression of multiple diseases, providing new opportunities for targeted treatment and a better understanding of disease pathogenesis.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Neurosciences
Runjiao Zhang, Yizhou Zhang, Fangzhen Guo, Sha Li, Huixian Cui
Summary: Epitranscriptomics, particularly RNA methylation modifications like N6-methyladenosine (m(6)A), play a crucial role in regulating gene expression. m(6)A, the most common and abundant type of eukaryotic RNA methylation modification, regulates nuclear splicing, stability, translation, and subcellular localization of RNAs. Increasing research has focused on the role of m(6)A modification in Alzheimer's disease.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
David Bade, Qian Cai, Lin Li, Kailin Yu, Xiaoxia Dai, Weili Miao, Yinsheng Wang
Summary: This study revealed a novel m(6)A-based epitranscriptomic mechanism in regulating protein N-terminal methylation, involving interactions between NTMT1 and reader/writer/eraser proteins associated with m(6)A.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Oncology
Hao-ze Shi, Jing-shu Xiong, Lu Gan, Ying Zhang, Cong-cong Zhang, Ying-qi Kong, Qiu-ju Miao, Cui-cui Tian, Rong Li, Jin-quan Liu, Er-jia Zhang, Wen-bo Bu, Yan Wang, Xian-feng Cheng, Jian-fang Sun, Hao Chen
Summary: This study found that m6A reader YTHDF3 plays an important role in the metastasis of melanoma. The downstream target of YTHDF3, LOXL3, was identified, and it was confirmed that YTHDF3 regulates the transcript of LOXL3 through m6A binding sites. Overexpression of LOXL3 weakened the inhibitory effect of YTHDF3 downregulation on melanoma metastasis.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Review
Hematology
Eliza Yankova, Demetrios Aspris, Konstantinos Tzelepis
Summary: Recent studies have shown that the m(6)A modification of RNA plays a crucial role in the development of acute myeloid leukemia (AML) and the maintenance of leukemic stem cells (LSCs). Various m(6)A regulators have been identified as potential translational targets for AML treatment, with promising therapeutic potential. The field of epitranscriptomics is still evolving, and therapeutics targeting RNA-modifying enzymes may offer new treatment avenues for malignancies like AML.
CURRENT OPINION IN HEMATOLOGY
(2021)
Review
Endocrinology & Metabolism
Caiqin Cheng, Fan Yu, Guoyue Yuan, Jue Jia
Summary: This review summarizes the latest research findings on the role of m6A methylation in obesity and related metabolic diseases. The study suggests that m6A modifications and corresponding regulators play a significant role in lipid metabolism and are closely associated with the pathogenesis of obesity-related diseases.
Article
Biochemistry & Molecular Biology
Kurtis Breger, Jessica A. Brown
Summary: Methyltransferase-like protein 16 (METTL16) is one of the four catalytically active m6A RNA methyltransferases in humans. This study investigated the kinetic mechanism and biochemical properties of METTL16. The results showed that METTL16 binds to U6 snRNA and the MALAT1 triple helix with high affinity, and the binding occurs in an ordered-sequential mechanism. The findings provide insights into the catalytic activity of METTL16 in biological functions.
Article
Biochemistry & Molecular Biology
Kristen R. Carraway, Ellen M. Johnson, Travis C. Kauffmann, Nate J. Fry, Kyle D. Mansfield
Article
Biochemistry & Molecular Biology
Nate J. Fry, Brittany A. Law, Olga R. Ilkayeva, Christopher L. Holley, Kyle D. Mansfield
Article
Multidisciplinary Sciences
Daniel J. Nance, Emily R. Satterwhite, Brinda Bhaskar, Sway Misra, Kristen R. Carraway, Kyle D. Mansfield
Article
Biochemistry & Molecular Biology
Emily S. Talic, Ashley Wooten, Tonya N. Zeczycki, Kyle D. Mansfield
Summary: METTL16 is a human m6A RNA methyltransferase known for modifying U6 and MAT2A RNAs. It is unclear whether it modifies other RNAs and the importance of its different RNA-binding domains. By mutating specific domains of METTL16 protein, we observed changes in RNA-binding ability, cell processes, and proliferation.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)