{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T08:32:35Z","timestamp":1793867555409,"version":"4.6.1"},"reference-count":129,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2024YFA1802700"],"award-info":[{"award-number":["2024YFA1802700"]}]},{"name":"National Key Research and Development Program of China","award":["82474017"],"award-info":[{"award-number":["82474017"]}]},{"name":"National Natural Science Foundation of China","award":["2024YFA1802700"],"award-info":[{"award-number":["2024YFA1802700"]}]},{"name":"National Natural Science Foundation of China","award":["82474017"],"award-info":[{"award-number":["82474017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>A variety of epigenetic mechanisms\u2014such as DNA methylation, histone alterations, RNA chemical modifications, and regulatory non-coding RNAs\u2014collectively influence gene regulation and cellular processes. Among these, N6-methyladenosine (m6A) represents the most widespread internal modification in eukaryotic mRNA, exerting significant influence on RNA metabolic pathways and modulating mRNA function at multiple levels. Studies have shown that m6A modification is highly enriched in the brain and regulates central nervous system development and various physiological functions. Recent studies have demonstrated that m6A interacts with other epigenetic regulators and triggers epigenetic remodeling, which further affects the development and occurrence of central nervous system diseases. In this review, we provide an up-to-date overview of this emerging research hotspot in biology, with a focus on the interplay between m6A and other epigenetic regulators. We highlight their potential roles and regulatory mechanisms in epigenetic reprogramming during central nervous system development and disease, offering insights into potential novel targets and therapeutic strategies for CNS disorders.<\/jats:p>","DOI":"10.3390\/biom15081092","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T10:51:14Z","timestamp":1753699874000},"page":"1092","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Crosstalk Between N6-Methyladenosine and Other Epigenetic Mechanisms in Central Nervous System Development and Disorders"],"prefix":"10.3390","volume":"15","author":[{"given":"Cuiping","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuping","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5300-8661","authenticated-orcid":false,"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, China"},{"name":"Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4408-2469","authenticated-orcid":false,"given":"Dan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China"},{"name":"Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41576-023-00645-2","article-title":"RNA modifications in physiology and disease: Towards clinical applications","volume":"25","author":"Delaunay","year":"2024","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lu, Z., Lyu, Z., Dong, P., Liu, Y., and Huang, L. (2025). N6-methyladenosine RNA modification in stomach carcinoma: Novel insights into mechanisms and implications for diagnosis and treatment. Biochim. Biophys. Acta\u2013Mol. Basis Dis., 1871.","DOI":"10.1016\/j.bbadis.2025.167793"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5119","DOI":"10.1038\/s41467-025-60447-4","article-title":"Single-molecule direct RNA sequencing reveals the shaping of epitranscriptome across multiple species","volume":"16","author":"Xie","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"123355","DOI":"10.1016\/j.lfs.2024.123355","article-title":"The role and mechanism of m6A methylation in diabetic nephropathy","volume":"363","author":"Yan","year":"2025","journal-title":"Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Luo, Z., Lou, L., Qiu, W., Xu, Z., and Xiao, X. (2022). Predicting N6-Methyladenosine Sites in Multiple Tissues of Mammals through Ensemble Deep Learning. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415490"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/j.cell.2020.05.012","article-title":"A Unified Model for the Function of YTHDF Proteins in Regulating m6A-Modified mRNA","volume":"181","author":"Zaccara","year":"2020","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.molcel.2019.04.025","article-title":"Where, When, and How: Context-Dependent Functions of RNA Methylation Writers, Readers, and Erasers","volume":"74","author":"Shi","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/s41556-018-0174-4","article-title":"m6A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer","volume":"20","author":"Liu","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41583-019-0244-z","article-title":"The m6A epitranscriptome: Transcriptome plasticity in brain development and function","volume":"21","author":"Livneh","year":"2020","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"eadq4623","DOI":"10.1126\/sciadv.adq4623","article-title":"Identification and characterization of the de novo methyltransferases for eukaryotic N6-methyladenine (6mA)","volume":"11","author":"Cheng","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41421-024-00756-y","article-title":"Mettl3-m6A-NPY axis governing neuron\u2013microglia interaction regulates sleep amount of mice","volume":"11","author":"Sun","year":"2025","journal-title":"Cell Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111693","DOI":"10.1016\/j.celrep.2022.111693","article-title":"m6A-modified lincRNA Dubr is required for neuronal development by stabilizing YTHDF1\/3 and facilitating mRNA translation","volume":"41","author":"Huang","year":"2022","journal-title":"Cell Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.gpb.2018.12.007","article-title":"m6A Regulates Neurogenesis and Neuronal Development by Modulating Histone Methyltransferase Ezh2","volume":"17","author":"Chen","year":"2019","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1101\/gr.278424.123","article-title":"Single-cell discovery of m6A RNA modifications in the hippocampus","volume":"34","author":"Feng","year":"2024","journal-title":"Genome Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Eun, J.W., Cheong, J.Y., Jeong, J.-Y., and Kim, H.S. (2023). A New Understanding of Long Non-Coding RNA in Hepatocellular Carcinoma\u2014From m6A Modification to Blood Biomarkers. Cells, 12.","DOI":"10.3390\/cells12182272"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1177\/0271678X20960033","article-title":"Epitranscriptomic regulation by m6A RNA methylation in brain development and diseases","volume":"40","author":"Chokkalla","year":"2020","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Dermentzaki, G., and Lotti, F. (2020). New Insights on the Role of N6-Methyladenosine RNA Methylation in the Physiology and Pathology of the Nervous System. Front. Mol. Biosci., 7.","DOI":"10.3389\/fmolb.2020.555372"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e0099722","DOI":"10.1128\/jvi.00997-22","article-title":"WTAP Targets the METTL3 m6A-Methyltransferase Complex to Cytoplasmic Hepatitis C Virus RNA to Regulate Infection","volume":"96","author":"Sacco","year":"2022","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e1829","DOI":"10.1002\/wrna.1829","article-title":"RNA m6A modifications regulate crosstalk between tumor metabolism and immunity","volume":"15","author":"Gu","year":"2024","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e1681","DOI":"10.1002\/wrna.1681","article-title":"RNA methyltransferase METTL16: Targets and function","volume":"13","author":"Satterwhite","year":"2022","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Azzam, S.K., Alsafar, H., and Sajini, A.A. (2022). FTO m6A Demethylase in Obesity and Cancer: Implications and Underlying Molecular Mechanisms. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073800"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gao, Z., Zha, X., Li, M., Xia, X., and Wang, S. (2024). Insights into the m6A demethylases FTO and ALKBH5: Structural, biological function, and inhibitor development. Cell Biosci., 14.","DOI":"10.1186\/s13578-024-01286-6"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nabeel-Shah, S., Pu, S., Burke, G.L., Ahmed, N., Braunschweig, U., Farhangmehr, S., Lee, H., Wu, M., Ni, Z., and Tang, H. (2024). Recruitment of the m6A\/m6Am demethylase FTO to target RNAs by the telomeric zinc finger protein ZBTB. Genome Biol., 25.","DOI":"10.1186\/s13059-024-03392-7"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.molcel.2018.08.011","article-title":"Differential m6A, m6Am, and m1A Demethylation Mediated by FTO in the Cell Nucleus and Cytoplasm","volume":"71","author":"Wei","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1038\/s41467-021-21758-4","article-title":"FTO-mediated cytoplasmic m6Am demethylation adjusts stem-like properties in colorectal cancer cell","volume":"12","author":"Relier","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7141","DOI":"10.1038\/s41380-021-01282-z","article-title":"Modifying the m6A brain methylome by ALKBH5-mediated demethylation: A new contender for synaptic tagging","volume":"26","author":"Markus","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.1093\/nar\/gkab415","article-title":"Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response","volume":"49","author":"Yu","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"108598","DOI":"10.1016\/j.celrep.2020.108598","article-title":"Ythdf m6A Readers Function Redundantly during Zebrafish Development","volume":"33","author":"Kontur","year":"2020","journal-title":"Cell Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Xu, Y., Zhang, W., Shen, F., Yang, X., Liu, H., Dai, S., Sun, X., Huang, J., and Guo, Q. (2021). YTH Domain Proteins: A Family of m6A Readers in Cancer Progression. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.629560"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4576","DOI":"10.1016\/j.molcel.2024.10.033","article-title":"m6A sites in the coding region trigger translation-dependent mRNA decay","volume":"84","author":"Zhou","year":"2024","journal-title":"Mol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111317","DOI":"10.1016\/j.celrep.2022.111317","article-title":"m1A and m6A modifications function cooperatively to facilitate rapid mRNA degradation","volume":"40","author":"Boo","year":"2022","journal-title":"Cell Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13045-020-00872-8","article-title":"m6A-binding proteins: The emerging crucial performers in epigenetics","volume":"13","author":"Zhao","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mathoux, J., Henshall, D.C., and Brennan, G.P. (2021). Regulatory Mechanisms of the RNA Modification m6A and Significance in Brain Function in Health and Disease. Front. Cell. Neurosci., 15.","DOI":"10.3389\/fncel.2021.671932"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.semcancer.2022.05.009","article-title":"The IGF2BP family of RNA binding proteins links epitranscriptomics to cancer","volume":"86","author":"Guil","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/nsmb.3462","article-title":"N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis","volume":"24","author":"Edupuganti","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e82703","DOI":"10.7554\/eLife.82703","article-title":"Nuclear m6A reader YTHDC1 promotes muscle stem cell activation\/proliferation by regulating mRNA splicing and nuclear export","volume":"12","author":"Qiao","year":"2023","journal-title":"eLife"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.molcel.2019.07.005","article-title":"Regulation of Co-transcriptional Pre-mRNA Splicing by m6A through the Low-Complexity Protein hnRNPG","volume":"76","author":"Zhou","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e31311","DOI":"10.7554\/eLife.31311","article-title":"YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs","volume":"6","author":"Roundtree","year":"2017","journal-title":"eLife"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"19889","DOI":"10.1074\/jbc.AC119.010078","article-title":"The RNA-binding protein FMRP facilitates the nuclear export of N6-methyladenosine-containing mRNAs","volume":"294","author":"Hsu","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5845","DOI":"10.1038\/s41467-022-32963-0","article-title":"Autophagy induction promoted by m6A reader YTHDF3 through translation upregulation of FOXO3 mRNA","volume":"13","author":"Hao","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.3324\/haematol.2021.279739","article-title":"YTHDF3 modulates hematopoietic stem cells by recognizing RNA m6A modification on Ccnd1","volume":"107","author":"Zhang","year":"2022","journal-title":"Haematologica"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3816","DOI":"10.1093\/nar\/gkaa048","article-title":"The m6A reader YTHDF1 promotes ovarian cancer progression via augmenting EIF3C translation","volume":"48","author":"Liu","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1093\/jmcb\/mjaa018","article-title":"eIF-Three to Tango: Emerging functions of translation initiation factor eIF3 in protein synthesis and disease","volume":"12","author":"Wolf","year":"2020","journal-title":"J. Mol. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"jcs248476","DOI":"10.1242\/jcs.248476","article-title":"Translation initiation in cancer at a glance","volume":"134","author":"Smith","year":"2021","journal-title":"J. Cell Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.tig.2019.12.007","article-title":"Molecular Mechanisms Driving mRNA Degradation by m6A Modification","volume":"36","author":"Lee","year":"2020","journal-title":"Trends Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.molcel.2019.02.034","article-title":"Endoribonucleolytic Cleavage of m6A-Containing RNAs by RNase P\/MRP Complex","volume":"74","author":"Park","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_47","first-page":"3936","article-title":"Fragile X mental retardation protein modulates the stability of its m6A-marked messenger RNA targets","volume":"27","author":"Zhang","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Liu, Z., Deng, K., Su, Y., Zhang, Z., Shi, C., Wang, J., Fan, Y., Zhang, G., and Wang, F. (2024). IGF2BP1-mediated the stability and protein translation of FGFR1 mRNA regulates myogenesis through the ERK signaling pathway. Int. J. Biol. Macromol., 280.","DOI":"10.1016\/j.ijbiomac.2024.135989"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Xu, Y., Xu, L., Kong, Y., Li, K., Li, J., Xu, F., Liang, S., and Chen, B. (2023). IGF2BP1 enhances the stability of SIK2 mRNA through m6A modification to promote non-small cell lung cancer progression. Biochem. Biophys. Res. Commun., 684.","DOI":"10.1016\/j.bbrc.2023.10.045"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.cell.2017.09.003","article-title":"Temporal Control of Mammalian Cortical Neurogenesis by m6A Methylation","volume":"171","author":"Yoon","year":"2017","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Li, M., Zhao, X., Wang, W., Shi, H., Pan, Q., Lu, Z., Perez, S.P., Suganthan, R., He, C., and Bj\u00f8r\u00e5s, M. (2018). 2-mediated m6A mRNA clearance modulates neural development in mice. Genome Biol., 19.","DOI":"10.1186\/s13059-018-1436-y"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41422-018-0113-8","article-title":"A novel m6A reader Prrc2a controls oligodendroglial specification and myelination","volume":"29","author":"Wu","year":"2019","journal-title":"Cell Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.neuron.2019.12.013","article-title":"m6A mRNA Methylation Is Essential for Oligodendrocyte Maturation and CNS Myelination","volume":"105","author":"Xu","year":"2020","journal-title":"Neuron"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"128099","DOI":"10.1016\/j.jhazmat.2021.128099","article-title":"Protective role of mRNA demethylase FTO on axon guidance molecules of nigro-striatal projection system in manganese-induced parkinsonism","volume":"426","author":"Qi","year":"2022","journal-title":"J. Hazard. Mater."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4765","DOI":"10.1093\/nar\/gkz157","article-title":"The m6A reader YTHDF1 regulates axon guidance through translational control of Robo3.1 expression","volume":"47","author":"Zhuang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6771","DOI":"10.1523\/JNEUROSCI.4053-15.2016","article-title":"Experience-Dependent Accumulation of N6 -Methyladenosine in the Prefrontal Cortex Is Associated with Memory Processes in Mice","volume":"36","author":"Widagdo","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1038\/npp.2017.31","article-title":"The Role of The RNA Demethylase FTO (Fat Mass and Obesity-Associated) and mRNA Methylation in Hippocampal Memory Formation","volume":"42","author":"Walters","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1093\/ijnp\/pyac068","article-title":"M6A RNA Methylation-Based Epitranscriptomic Modifications in Plasticity-Related Genes via miR-124-C\/EBP\u03b1-FTO-Transcriptional Axis in the Hippocampus of Learned Helplessness Rats","volume":"25","author":"Roy","year":"2022","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Liu, S.-J., Cai, T.-H., Fang, C.-L., Lin, S.-Z., Yang, W.-Q., Wei, Y., Zhou, F., Liu, L., Luo, Y., and Guo, Z.-Y. (2022). Long-term exercise training down-regulates m6A RNA demethylase FTO expression in the hippocampus and hypothalamus: An effective intervention for epigenetic modification. BMC Neurosci., 23.","DOI":"10.1186\/s12868-022-00742-8"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3759","DOI":"10.1007\/s12035-021-02363-4","article-title":"Comprehensive Analysis of Differential m6A RNA Methylomes in the Hippocampus of Cocaine-Conditioned Mice","volume":"58","author":"Xue","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"721","DOI":"10.7150\/thno.31562","article-title":"Fto Deficiency Reduces Anxiety- and Depression-Like Behaviors in Mice via Alterations in Gut Microbiota","volume":"9","author":"Sun","year":"2019","journal-title":"Theranostics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/s41422-018-0092-9","article-title":"METTL3-mediated N6-methyladenosine mRNA modification enhances long-term memory consolidation","volume":"28","author":"Zhang","year":"2018","journal-title":"Cell Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41583-018-0088-y","article-title":"Rhythms of life: Circadian disruption and brain disorders across the lifespan","volume":"20","author":"Logan","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.cell.2013.10.026","article-title":"RNA-Methylation-Dependent RNA Processing Controls the Speed of the Circadian Clock","volume":"155","author":"Fustin","year":"2013","journal-title":"Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"dev182683","DOI":"10.1242\/dev.182683","article-title":"Mammalian DNA methylome dynamics: Mechanisms, functions and new frontiers","volume":"149","author":"Wei","year":"2022","journal-title":"Development"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1146\/annurev-biochem-103019-102815","article-title":"Role of Mammalian DNA Methyltransferases in Development","volume":"89","author":"Chen","year":"2020","journal-title":"Annu. Rev. Biochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1126\/science.1063852","article-title":"The Role of DNA Methylation in Mammalian Epigenetics","volume":"293","author":"Jones","year":"2001","journal-title":"Science"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1126\/science.1170116","article-title":"Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET","volume":"324","author":"Tahiliani","year":"2009","journal-title":"Science"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1126\/science.1210597","article-title":"Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine and 5-Carboxylcytosine","volume":"333","author":"Ito","year":"2011","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Zhou, L., Tian, S., and Qin, G. (2019). RNA methylomes reveal the m6A-mediated regulation of DNA demethylase gene SlDML2 in tomato fruit ripening. Genome Biol., 20.","DOI":"10.1186\/s13059-019-1771-7"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1038\/s41467-019-09712-x","article-title":"Excessive miR-25-3p maturation via N6-methyladenosine stimulated by cigarette smoke promotes pancreatic cancer progression","volume":"10","author":"Zhang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1158\/0008-5472.CAN-19-3440","article-title":"A Novel Micropeptide Encoded by Y-Linked LINC00278 Links Cigarette Smoking and AR Signaling in Male Esophageal Squamous Cell Carcinoma","volume":"80","author":"Wu","year":"2020","journal-title":"Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12038-020-00099-2","article-title":"Evaluation of post-translational modifications in histone proteins: A review on histone modification defects in developmental and neurological disorders","volume":"45","author":"Ramazi","year":"2020","journal-title":"J. Biosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/s41588-020-0677-3","article-title":"N6-Methyladenosine co-transcriptionally directs the demethylation of histone H3K9me","volume":"52","author":"Li","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"6454","DOI":"10.1126\/science.aav0758","article-title":"Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to DNA viruses","volume":"365","author":"Wang","year":"2019","journal-title":"Science"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12943-018-0766-4","article-title":"New insights into the regulatory role of microRNA in tumor angiogenesis and clinical implications","volume":"17","author":"Wang","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/nature14281","article-title":"N6-methyladenosine marks primary microRNAs for processing","volume":"519","author":"Lee","year":"2015","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1038\/s41418-019-0461-z","article-title":"IGF2BP2 regulates DANCR by serving as an N6-methyladenosine reader","volume":"27","author":"Hu","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s12943-019-1036-9","article-title":"METTL3 promote tumor proliferation of bladder cancer by accelerating pri-miR221\/222 maturation in m6A-dependent manner","volume":"18","author":"Han","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1038\/s41419-018-1132-6","article-title":"circRNA_104075 stimulates YAP-dependent tumorigenesis through the regulation of HNF4a and may serve as a diagnostic marker in hepatocellular carcinoma","volume":"9","author":"Zhang","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e12768","DOI":"10.1111\/cpr.12768","article-title":"Cross talk between RNA N6-methyladenosine methyltransferase-like 3 and miR-186 regulates hepatoblastoma progression through Wnt\/\u03b2-catenin signalling pathway","volume":"53","author":"Cui","year":"2020","journal-title":"Cell Prolif."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nrm.2017.104","article-title":"The functions and unique features of long intergenic non-coding RNA","volume":"19","author":"Ransohoff","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13045-019-0839-x","article-title":"M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma","volume":"13","author":"Zuo","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s12943-022-01572-2","article-title":"The m6A demethylase ALKBH5 promotes tumor progression by inhibiting RIG-I expression and interferon alpha production through the IKK\u03b5\/TBK1\/IRF3 pathway in head and neck squamous cell carcinoma","volume":"21","author":"Jin","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12943-022-01522-y","article-title":"Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification","volume":"21","author":"Hu","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3906","DOI":"10.1093\/nar\/gky130","article-title":"N6-Methyladenosine modification of lincRNA 1281 is critically required for mESC differentiation potential","volume":"46","author":"Yang","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6051","DOI":"10.1093\/nar\/gkx141","article-title":"N6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein","volume":"45","author":"Liu","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.15252\/embr.201744940","article-title":"Human METTL16 is a N6-methyladenosine (m6A) methyltransferase that targets pre-mRNAs and various non-coding RNAs","volume":"18","author":"Warda","year":"2017","journal-title":"EMBO Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13045-021-01048-8","article-title":"m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis","volume":"14","author":"Jin","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nrm.2015.32","article-title":"The biogenesis and emerging roles of circular RNAs","volume":"17","author":"Chen","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1016\/j.celrep.2017.08.027","article-title":"Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs","volume":"20","author":"Zhou","year":"2017","journal-title":"Cell Rep."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"107641","DOI":"10.1016\/j.celrep.2020.107641","article-title":"Modulation of circRNA Metabolism by m6A Modification","volume":"31","author":"Dattilo","year":"2020","journal-title":"Cell Rep."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41422-020-0279-8","article-title":"m6A-dependent biogenesis of circular RNAs in male germ cells","volume":"30","author":"Tang","year":"2020","journal-title":"Cell Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4695","DOI":"10.1038\/s41467-019-12651-2","article-title":"N6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis","volume":"10","author":"Chen","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.molcel.2019.07.016","article-title":"N6-Methyladenosine Modification Controls Circular RNA Immunity","volume":"76","author":"Chen","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Jia, Z., and Wu, Q. (2019). Clustered Protocadherins Emerge as Novel Susceptibility Loci for Mental Disorders. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.587819"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41398-020-01173-x","article-title":"Structural diverseness of neurons between brain areas and between cases","volume":"11","author":"Mizutani","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/s41593-017-0057-1","article-title":"N6-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications","volume":"21","author":"Wang","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/S0140-6736(21)02143-7","article-title":"Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic","volume":"398","author":"Santomauro","year":"2021","journal-title":"Lancet"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jad.2020.11.117","article-title":"Prevalence of mental health problems during the COVID-19 pandemic: A systematic review and meta-analysis","volume":"281","author":"Wu","year":"2021","journal-title":"J. Affect. Disord."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1177\/00048674221086498","article-title":"Correlates of suicidality in young people with depressive disorders: A systematic review","volume":"56","author":"Moller","year":"2022","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"9759","DOI":"10.1007\/s11033-022-07461-7","article-title":"Synaptic plasticity and depression: The role of miRNAs dysregulation","volume":"49","author":"Rahmani","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41398-020-01159-9","article-title":"Molecular pathology associated with altered synaptic transcriptome in the dorsolateral prefrontal cortex of depressed subjects","volume":"11","author":"Yoshino","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1038\/s41380-022-01520-y","article-title":"Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications","volume":"27","author":"Tartt","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ajp.2017.01.025","article-title":"The neurobiology of depression: An integrated view","volume":"27","author":"Dean","year":"2017","journal-title":"Asian J. Psychiatry"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.neubiorev.2019.04.011","article-title":"Motivation and cognitive control in depression","volume":"102","author":"Grahek","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/ajmg.b.32892","article-title":"Mechanism of METTL3-mediated m6A modification in depression-induced cognitive deficits","volume":"189","author":"Niu","year":"2022","journal-title":"Am. J. Med. Genetics Part B Neuropsychiatr. Genet. Off. Publ. Int. Soc. Psychiatr. Genetics"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.biopsych.2020.02.018","article-title":"N6-Methyladenosine Modification of Fatty Acid Amide Hydrolase Messenger RNA in Circular RNA STAG1-Regulated Astrocyte Dysfunction and Depressive-like Behaviors","volume":"88","author":"Huang","year":"2020","journal-title":"Biol. Psychiatry"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Vitovcova, B., Skarkova, V., Rudolf, K., and Rudolf, E. (2020). Biology of Glioblastoma Multiforme\u2014Exploration of Mitotic Catastrophe as a Potential Treatment Modality. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155324"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Thomas, L., Florio, T., and Perez-Castro, C. (2020). Extracellular Vesicles Loaded miRNAs as Potential Modulators Shared Between Glioblastoma, and Parkinson\u2019s and Alzheimer\u2019s Diseases. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.590034"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/cas.12379","article-title":"Epigenetic dysregulation in glioma","volume":"105","author":"Kondo","year":"2014","journal-title":"Cancer Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e553","DOI":"10.1002\/ctm2.553","article-title":"Interplay of m6A and histone modifications contributes to temozolomide resistance in glioblastoma","volume":"11","author":"Li","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e424","DOI":"10.1002\/ctm2.424","article-title":"Histone demethylase JMJD1C promotes the polarization of M1 macrophages to prevent glioma by upregulating miR-302a","volume":"11","author":"Zhong","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/s41420-021-00674-y","article-title":"m6A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability","volume":"7","author":"Liu","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s10143-020-01238-x","article-title":"Identification of N6-methyladenosine-related lncRNAs for patients with primary glioblastoma","volume":"44","author":"Wang","year":"2021","journal-title":"Neurosurg. Rev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"7348","DOI":"10.18632\/aging.204177","article-title":"RP11-552D4.1: A novel m6a-related LncRNA associated with immune status in glioblastoma","volume":"14","author":"Zheng","year":"2022","journal-title":"Aging"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Xie, P., Yan, H., Gao, Y., Li, X., Zhou, D.-B., and Liu, Z.-Q. (2022). Construction of m6A-Related lncRNA Prognostic Signature Model and Immunomodulatory Effect in Glioblastoma Multiforme. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.920926"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"771","DOI":"10.30773\/pi.2021.0370","article-title":"m6A Methyltransferase METTL3 Reduces Hippocampal Neuron Apoptosis in a Mouse Model of Autism Through the MALAT1\/SFRP2\/Wnt\/\u03b2-catenin Axis","volume":"19","author":"Ming","year":"2022","journal-title":"Psychiatry Investig."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.toxlet.2018.04.002","article-title":"Paraquat and MPTP induce alteration in the expression profile of long noncoding RNAs in the substantia nigra of mice: Role of the transcription factor Nrf","volume":"291","author":"Wang","year":"2018","journal-title":"Toxicol. Lett."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"113503","DOI":"10.1016\/j.ecoenv.2022.113503","article-title":"Paraquat-induced oxidative stress regulates N6-methyladenosine (m6A) modification of long noncoding RNAs in Neuro-2a cells","volume":"237","author":"Su","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1111\/j.1747-4949.2009.00387.x","article-title":"Oxidative stress and its role in the pathogenesis of ischaemic stroke","volume":"4","author":"Allen","year":"2009","journal-title":"Int. J. Stroke Off. J. Int. Stroke Soc."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"25640","DOI":"10.18632\/oncotarget.8241","article-title":"Argon protects against hypoxic-ischemic brain injury in neonatal rats through activation of nuclear factor (erythroid-derived 2)-like","volume":"7","author":"Zhao","year":"2016","journal-title":"Oncotarget"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/s41419-020-03021-8","article-title":"Oxygen glucose deprivation\/re-oxygenation-induced neuronal cell death is associated with Lnc-D63785 m6A methylation and miR-422a accumulation","volume":"11","author":"Xu","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/s41586-021-03536-w","article-title":"Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia","volume":"593","author":"Yankova","year":"2021","journal-title":"Nature"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Malacrida, A., Rivara, M., Di Domizio, A., Cislaghi, G., Miloso, M., Zuliani, V., and Nicolini, G. (2020). 3D proteome-wide scale screening and activity evaluation of a new ALKBH5 inhibitor in U87 glioblastoma cell line. Bioorganic Med. Chem., 28.","DOI":"10.1016\/j.bmc.2019.115300"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/cbdd.14051","article-title":"Discovery of two novel ALKBH5 selective inhibitors that exhibit uncompetitive or competitive type and suppress the growth activity of glioblastoma multiforme","volume":"100","author":"Takahashi","year":"2022","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Li, R., Kuang, Y., Niu, Y., Zhang, S., Chen, S., Su, F., Wang, J., Lin, S., Liu, D., and Shen, C. (2024). FTO-mediated RNA m6A methylation regulates synovial aggression and inflammation in rheumatoid arthritis. Biochim. et Biophys. Acta\u2013-Mol. Basis Dis., 1870.","DOI":"10.1016\/j.bbadis.2024.167341"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s13148-023-01568-9","article-title":"METTL3 exerts synergistic effects on m6A methylation and histone modification to regulate the function of VGF in lung adenocarcinoma","volume":"15","author":"Shi","year":"2023","journal-title":"Clin. Epigenet."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Deng, J., Chen, X., Chen, A., and Zheng, X. (2022). m6A RNA methylation in brain injury and neurodegenerative disease. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.995747"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/8\/1092\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:17:16Z","timestamp":1760033836000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/8\/1092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,28]]},"references-count":129,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["biom15081092"],"URL":"https:\/\/doi.org\/10.3390\/biom15081092","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,28]]}}}