Novel insight into RNA modifications in tumor immunity: Promising targets to prevent tumor immune escape

The Innovation - Tập 4 - Trang 100452 - 2023
Yuxin Kong1, Jie Yu1, Shengfang Ge1, Xianqun Fan1
1Department of Ophthalmology, Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200001, China

Tài liệu tham khảo

Davis, 1957, Ribonucleic acids from yeast which contain a fifth nucleotide, J. Biol. Chem., 227, 907, 10.1016/S0021-9258(18)70770-9 Roundtree, 2017, Dynamic RNA modifications in gene expression regulation, Cell, 169, 1187, 10.1016/j.cell.2017.05.045 Shima, 2020, N 1-methyladenosine (m1A) RNA modification: the key to ribosome control, J. Biochem., 167, 535, 10.1093/jb/mvaa026 Wang, 2015, N6-methyladenosine modulates messenger RNA translation efficiency, Cell, 161, 1388, 10.1016/j.cell.2015.05.014 Bohnsack, 2019, Eukaryotic 5-methylcytosine (m5C) RNA methyltransferases: mechanisms, cellular functions, and links to disease, Genes, 10, 102, 10.3390/genes10020102 Enroth, 2019, Detection of internal N7-methylguanosine (m7G) RNA modifications by mutational profiling sequencing, Nucleic Acids Res., 47, e126, 10.1093/nar/gkz736 Cowling, 2010, Regulation of mRNA cap methylation, Biochem. J., 425, 295, 10.1042/BJ20091352 Charette, 2000, Pseudouridine in RNA: what, where, how, and why, IUBMB Life, 49, 341, 10.1080/152165400410182 De Almeida, 2018, RNA uridylation: a key posttranscriptional modification shaping the coding and noncoding transcriptome, Wiley Interdiscip. Rev. RNA, 9, 10.1002/wrna.1440 Du, 2016, YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4–NOT deadenylase complex, Nat. Commun., 7, 12626, 10.1038/ncomms12626 Park, 2019, Endoribonucleolytic cleavage of m6A-containing RNAs by RNase P/MRP complex, Mol. Cell, 74, 494, 10.1016/j.molcel.2019.02.034 Zhang, 2018, Fragile X mental retardation protein modulates the stability of its m6A-marked messenger RNA targets, Hum. Mol. Genet., 27, 3936 Kasowitz, 2018, Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development, PLoS Genet., 14, 10.1371/journal.pgen.1007412 Roundtree, 2017, YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs, Elife, 6, 10.7554/eLife.31311 Huang, 2018, Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation, Nat. Cell Biol., 20, 285, 10.1038/s41556-018-0045-z Wang, 2018, METTL3-mediated m6A modification is required for cerebellar development, PLoS Biol., 16, 10.1371/journal.pbio.2004880 Hsu, 2017, Ythdc2 is an N6-methyladenosine binding protein that regulates mammalian spermatogenesis, Cell Res., 27, 1115, 10.1038/cr.2017.99 Hellmann, 2021, Entinostat plus pembrolizumab in patients with metastatic NSCLC previously treated with anti–PD-(L) 1 TherapyEntinostat plus pembrolizumab in previously treated mNSCLC, Clin. Cancer Res., 27, 1019, 10.1158/1078-0432.CCR-20-3305 Papadatos-Pastos, 2022, Phase 1, dose-escalation study of guadecitabine (SGI-110) in combination with pembrolizumab in patients with solid tumors, J. Immunother. cancer, 10 Yin, 2021, RNA m6A methylation orchestrates cancer growth and metastasis via macrophage reprogramming, Nat. Commun., 12, 1394, 10.1038/s41467-021-21514-8 Han, 2019, Anti-tumour immunity controlled through mRNA m6A methylation and YTHDF1 in dendritic cells, Nature, 566, 270, 10.1038/s41586-019-0916-x Gu, 2020, RNA m6A modification in cancers: molecular mechanisms and potential clinical applications, Innov, 1 Li, 2023, The role of RNA m6A modification in cancer glycolytic reprogramming, Curr. Gene Ther., 23, 51, 10.2174/1566523222666220830150446 Desrosiers, 1974, Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells, Proc. Natl. Acad. Sci. USA, 71, 3971, 10.1073/pnas.71.10.3971 Rottman, 1974, Sequences containing methylated nucleotides at the 5′ termini of messenger RNAs: possible implications for processing, Cell, 3, 197, 10.1016/0092-8674(74)90131-7 Meyer, 2012, Comprehensive analysis of mRNA methylation reveals enrichment in 3’ UTRs and near stop codons, Cell, 149, 1635, 10.1016/j.cell.2012.05.003 Yang, 2018, N 6-Methyladenosine modification of lincRNA 1281 is critically required for mESC differentiation potential, Nucleic Acids Res., 46, 3906, 10.1093/nar/gky130 Zhang, 2020, The role of N6-methyladenosine (m6A) modification in the regulation of circRNAs, Mol. Cancer, 19, 105, 10.1186/s12943-020-01224-3 Chen, 2019, WHISTLE: a high-accuracy map of the human N 6-methyladenosine (m6A) epitranscriptome predicted using a machine learning approach, Nucleic Acids Res., 47, e41, 10.1093/nar/gkz074 Zhou, 2016, SRAMP: prediction of mammalian N6-methyladenosine (m6A) sites based on sequence-derived features, Nucleic Acids Res., 44, e91, 10.1093/nar/gkw104 Huang, 2018, BERMP: a cross-species classifier for predicting m6A sites by integrating a deep learning algorithm and a random forest approach, Int. J. Biol. Sci., 14, 1669, 10.7150/ijbs.27819 Feng, 2017, iRNA-PseColl: identifying the occurrence sites of different RNA modifications by incorporating collective effects of nucleotides into PseKNC, Mol. Ther. Acids, 7, 155, 10.1016/j.omtn.2017.03.006 Zou, 2019, Gene2vec: gene subsequence embedding for prediction of mammalian N6-methyladenosine sites from mRNA, Rna, 25, 205, 10.1261/rna.069112.118 Chen, 2018, Analytical methods for deciphering RNA modifications, Anal. Chem., 91, 743, 10.1021/acs.analchem.8b04078 Zhao, 2020, Mapping the epigenetic modifications of DNA and RNA, Protein Cell, 11, 792, 10.1007/s13238-020-00733-7 Moshitch-Moshkovitz, 2022, The epitranscriptome toolbox, Cell, 185, 764, 10.1016/j.cell.2022.02.007 Buck, 1983, Complete analysis of tRNA-modified nucleosides by high-performance liquid chromatography: the 29 modified nucleosides of Salmonella typhimurium and Escherichia coli tRNA, Anal. Biochem., 129, 1, 10.1016/0003-2697(83)90044-1 Motorin, 2007, Identification of modified residues in RNAs by reverse transcription-based methods, Methods Enzymol., 425, 21, 10.1016/S0076-6879(07)25002-5 Grosjean, 2004, Detection and quantification of modified nucleotides in RNA using thin-layer chromatography, Methods Mol. Biol., 265, 357 Wetzel, 2016, Mass spectrometry of modified RNAs: recent developments, Analyst, 141, 16, 10.1039/C5AN01797A Schwartz, 2017, Next-generation sequencing technologies for detection of modified nucleotides in RNAs, RNA Biol., 14, 1124, 10.1080/15476286.2016.1251543 Tang, 2023, Mass spectrometry profiling analysis enables the identification of new modifications in ribosomal RNA, Chinese Chem. Lett., 34, 10.1016/j.cclet.2022.05.045 Chen, 2022, Adolescent alcohol exposure alters DNA and RNA modifications in peripheral blood by liquid chromatography-tandem mass spectrometry analysis, Chinese Chem. Lett., 33, 2086, 10.1016/j.cclet.2021.08.094 Chen, 2022, Comprehensive profiling and evaluation of the alteration of RNA modifications in thyroid carcinoma by liquid chromatography-tandem mass spectrometry, Chinese Chem. Lett., 33, 3772, 10.1016/j.cclet.2021.12.008 Wang, 2016, Structural basis of N6-adenosine methylation by the METTL3–METTL14 complex, Nature, 534, 575, 10.1038/nature18298 Wen, 2018, Zc3h13 regulates nuclear RNA m6A methylation and mouse embryonic stem cell self-renewal, Mol. Cell, 69, 1028, 10.1016/j.molcel.2018.02.015 Bokar, 1997, Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase, Rna, 3, 1233 Liu, 2014, A METTL3–METTL14 complex mediates mammalian nuclear RNA N 6-adenosine methylation, Nat. Chem. Biol., 10, 93, 10.1038/nchembio.1432 Ping, 2014, Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase, Cell Res., 24, 177, 10.1038/cr.2014.3 Warda, 2017, Human METTL16 is a N6-methyladenosine (m6A) methyltransferase that targets pre-mRNAs and various non-coding RNAs, EMBO Rep., 18, 2004, 10.15252/embr.201744940 Jia, 2011, N 6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO, Nat. Chem. Biol., 7, 885, 10.1038/nchembio.687 Zheng, 2013, ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility, Mol. Cell, 49, 18, 10.1016/j.molcel.2012.10.015 Liao, 2018, YTH domain: a family of N6-methyladenosine (m6A) readers, Dev. Reprod. Biol., 16, 99 Alarcón, 2015, HNRNPA2B1 is a mediator of m6A-dependent nuclear RNA processing events, Cell, 162, 1299, 10.1016/j.cell.2015.08.011 Liu, 2015, N6-methyladenosine-dependent RNA structural switches regulate RNA–protein interactions, Nature, 518, 560, 10.1038/nature14234 Arguello, 2017, RNA chemical proteomics reveals the N6-methyladenosine (m6A)-regulated protein–RNA interactome, J. Am. Chem. Soc., 139, 17249, 10.1021/jacs.7b09213 Edupuganti, 2017, N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis, Nat. Struct. Mol. Biol., 24, 870, 10.1038/nsmb.3462 Wu, 2019, A novel m6A reader Prrc2a controls oligodendroglial specification and myelination, Cell Res., 29, 23, 10.1038/s41422-018-0113-8 Li, 2017, Cytoplasmic m6A reader YTHDF3 promotes mRNA translation, Cell Res, 27, 444, 10.1038/cr.2017.10 Shi, 2017, YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA, Cell Res., 27, 315, 10.1038/cr.2017.15 Ries, 2019, m6A enhances the phase separation potential of mRNA, Nature, 571, 424, 10.1038/s41586-019-1374-1 Xiao, 2016, Nuclear m6A reader YTHDC1 regulates mRNA splicing, Mol. Cell, 61, 507, 10.1016/j.molcel.2016.01.012 Wojtas, 2017, Regulation of m6A transcripts by the 3ʹ→ 5ʹ RNA helicase YTHDC2 is essential for a successful meiotic program in the mammalian germline, Mol. Cell, 68, 374, 10.1016/j.molcel.2017.09.021 Zhang, 2022, Dynamic FMR1 granule phase switch instructed by m6A modification contributes to maternal RNA decay, Nat. Commun., 13, 859, 10.1038/s41467-022-28547-7 Hsu, 2019, The RNA-binding protein FMRP facilitates the nuclear export of N6-methyladenosine–containing mRNAs, J. Biol. Chem., 294, 19889, 10.1074/jbc.AC119.010078 Gu, 2021, DMDRMR-mediated regulation of m6A-modified CDK4 by m6A reader IGF2BP3 drives ccRCC progression, Cancer Res, 81, 923, 10.1158/0008-5472.CAN-20-1619 Patil, 2016, m6A RNA methylation promotes XIST-mediated transcriptional repression, Nature, 537, 369, 10.1038/nature19342 Liu, 2020, N 6-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription, Science, 367, 580, 10.1126/science.aay6018 Lee, 2021, Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation, Mol. Cell, 81, 3368, 10.1016/j.molcel.2021.07.024 Xu, 2022, Dynamic control of chromatin-associated m6A methylation regulates nascent RNA synthesis, Mol. Cell, 82, 1156, 10.1016/j.molcel.2022.02.006 Li, 2020, N6-Methyladenosine co-transcriptionally directs the demethylation of histone H3K9me2, Nat. Genet., 52, 870, 10.1038/s41588-020-0677-3 Cassetta, 2011, Macrophage polarization in health and disease, Sci. World J., 11, 2391, 10.1100/2011/213962 Murray, 2017, Macrophage polarization, Annu. Rev. Physiol., 79, 541, 10.1146/annurev-physiol-022516-034339 Liu, 2019, The N 6-methyladenosine (m6A)-forming enzyme METTL3 facilitates M1 macrophage polarization through the methylation of STAT1 mRNA, Am. J. Physiol. Physiol., 317, C762, 10.1152/ajpcell.00212.2019 Wang, 2021, The m6A reader IGF2BP2 regulates macrophage phenotypic activation and inflammatory diseases by stabilizing TSC1 and PPARγ, Adv. Sci., 8 Tong, 2021, Pooled CRISPR screening identifies m6A as a positive regulator of macrophage activation, Sci. Adv., 7, 10.1126/sciadv.abd4742 Gu, 2020, N6-methyladenosine demethylase FTO promotes M1 and M2 macrophage activation, Cell. Signal., 69, 10.1016/j.cellsig.2020.109553 Du, 2020, N6-Adenosine methylation of Socs1 mRNA is required to sustain the negative feedback control of macrophage activation, Dev. Cell, 55, 737, 10.1016/j.devcel.2020.10.023 Hu, 2022, N6-methyladenosine of Socs1 modulates macrophage inflammatory response in different stiffness environments, Int. J. Biol. Sci., 18, 5753, 10.7150/ijbs.74196 Pathria, 2019, Targeting tumor-associated macrophages in cancer, Trends Immunol., 40, 310, 10.1016/j.it.2019.02.003 Dong, 2021, The loss of RNA N6-adenosine methyltransferase Mettl14 in tumor-associated macrophages promotes CD8+ T cell dysfunction and tumor growth, Cancer Cell, 39, 945, 10.1016/j.ccell.2021.04.016 Liu, 2022, LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma, J. Hematol. Oncol., 15, 52, 10.1186/s13045-022-01272-w Xiong, 2022, Lactylation-driven METTL3-mediated RNA m6A modification promotes immunosuppression of tumor-infiltrating myeloid cells, Mol. Cell, 82, 1660, 10.1016/j.molcel.2022.02.033 Qian, 2018, Dendritic cells in the regulation of immunity and inflammation, Semin. Immunol., 35, 3, 10.1016/j.smim.2017.12.002 Wang, 2019, Mettl3-mediated mRNA m 6 A methylation promotes dendritic cell activation, Nat. Commun., 10, 1898, 10.1038/s41467-019-09903-6 Ulvmar, 2014, The atypical chemokine receptor CCRL1 shapes functional CCL21 gradients in lymph nodes, Nat. Immunol., 15, 623, 10.1038/ni.2889 Li, 2019, CCR7 chemokine receptor-inducible lnc-Dpf3 restrains dendritic cell migration by inhibiting HIF-1α-mediated glycolysis, Immunity, 43, 600, 10.1016/j.immuni.2019.01.021 Xiao, 2023, Nanodrug enhances post-ablation immunotherapy of hepatocellular carcinoma via promoting dendritic cell maturation and antigen presentation, Bioact. Mater., 21, 57, 10.1016/j.bioactmat.2022.07.027 Hodgins, 2019, Killers 2.0: NK cell therapies at the forefront of cancer control, J. Clin. Invest., 129, 3499, 10.1172/JCI129338 Smyth, 2000, Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma, J. Exp. Med., 192, 755, 10.1084/jem.192.5.755 Morandi, 2012, Dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response, PLoS One, 7, 10.1371/journal.pone.0039170 Böttcher, 2018, NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control, Cell, 172, 1022, 10.1016/j.cell.2018.01.004 Ma, 2021, The RNA m6A reader YTHDF2 controls NK cell antitumor and antiviral immunity, J. Exp. Med., 218, 10.1084/jem.20210279 Song, 2021, METTL3-mediated m6A RNA methylation promotes the anti-tumour immunity of natural killer cells, Nat. Commun., 12, 5522, 10.1038/s41467-021-25803-0 Li, 2016, T cell receptor signalling in the control of regulatory T cell differentiation and function, Nat. Rev. Immunol., 16, 220, 10.1038/nri.2016.26 Li, 2017, m6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways, Nature, 548, 338, 10.1038/nature23450 Tong, 2018, m6A mRNA methylation sustains Treg suppressive functions, Cell Res., 28, 253, 10.1038/cr.2018.7 Ito-Kureha, 2022, The function of Wtap in N6-adenosine methylation of mRNAs controls T cell receptor signaling and survival of T cells, Nat. Immunol., 23, 1208, 10.1038/s41590-022-01268-1 Zhou, 2021, m6A demethylase ALKBH5 controls CD4+ T cell pathogenicity and promotes autoimmunity, Sci. Adv., 7, 10.1126/sciadv.abg0470 Vinuesa, 2016, Follicular helper T cells, Annu. Rev. Immunol., 34, 335, 10.1146/annurev-immunol-041015-055605 Yao, 2021, METTL3-dependent m6A modification programs T follicular helper cell differentiation, Nat. Commun., 12, 1333, 10.1038/s41467-021-21594-6 Zhu, 2019, The E3 ligase VHL promotes follicular helper T cell differentiation via glycolytic-epigenetic control, J. Exp. Med., 216, 1664, 10.1084/jem.20190337 Ding, 2022, RNA m6A demethylase ALKBH5 regulates the development of γδ T cells, Proc. Natl. Acad. Sci. USA, 119, 10.1073/pnas.2203318119 Wan, 2022, METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating N6-methyladenosine modification of PD-L1 mRNA in breast cancer, Mol. Cancer, 21, 1, 10.1186/s12943-021-01447-y Ni, 2022, JNK signaling promotes bladder cancer immune escape by regulating METTL3-mediated m6A modification of PD-L1 mRNA, Cancer Res., 82, 1789, 10.1158/0008-5472.CAN-21-1323 Liu, 2021, N6-methyladenosine-modified circIGF2BP3 inhibits CD8+ T-cell responses to facilitate tumor immune evasion by promoting the deubiquitination of PD-L1 in non-small cell lung cancer, Mol. Cancer, 20, 105, 10.1186/s12943-021-01398-4 Zheng, 2022, Decreased expression of programmed death ligand-L1 by seven in absentia homolog 2 in cholangiocarcinoma enhances T-cell–mediated antitumor activity, Front. Immunol., 13, 845193, 10.3389/fimmu.2022.845193 Peng, 2022, Lipopolysaccharide facilitates immune escape of hepatocellular carcinoma cells via m6A modification of lncRNA MIR155HG to upregulate PD-L1 expression, Cell Biol. Toxicol., 38, 1159, 10.1007/s10565-022-09718-0 Liu, 2022, Allosteric regulation of IGF2BP1 as a novel strategy for the activation of tumor immune microenvironment, ACS Cent. Sci., 8, 1102, 10.1021/acscentsci.2c00107 Li, 2022, Methionine deficiency facilitates antitumour immunity by altering m6A methylation of immune checkpoint transcripts, Gut, 72, 501, 10.1136/gutjnl-2022-326928 Qiu, 2021, M6A demethylase ALKBH5 regulates PD-L1 expression and tumor immunoenvironment in intrahepatic cholangiocarcinoma, Cancer Res., 81, 4778, 10.1158/0008-5472.CAN-21-0468 Yang, 2019, m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade, Nat. Commun., 10, 2782, 10.1038/s41467-019-10669-0 Zhao, 2022, N6-Methyladenosine-Modified CBX1 regulates nasopharyngeal carcinoma progression through heterochromatin formation and STAT1 activation, Adv. Sci., 9, 10.1002/advs.202205091 Su, 2020, Targeting FTO suppresses cancer stem cell maintenance and immune evasion, Cancer Cell, 38, 79, 10.1016/j.ccell.2020.04.017 Bai, 2022, Loss of YTHDF1 in gastric tumors restores sensitivity to antitumor immunity by recruiting mature dendritic cells, J. Immunother. cancer, 10 Dey, 2021, Metabolic codependencies in the tumor microenvironment, Cancer Discov., 11, 1067, 10.1158/2159-8290.CD-20-1211 An, 2022, The role of m6A RNA methylation in cancer metabolism, Mol. Cancer, 21, 14, 10.1186/s12943-022-01500-4 Li, 2020, ALKBH5 regulates anti–PD-1 therapy response by modulating lactate and suppressive immune cell accumulation in tumor microenvironment, Proc. Natl. Acad. Sci. USA, 117, 20159, 10.1073/pnas.1918986117 Liu, 2021, Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance, Cell Metabol., 33, 1221, 10.1016/j.cmet.2021.04.001 Cai, 2022, CircRHBDD1 augments metabolic rewiring and restricts immunotherapy efficacy via m6A modification in hepatocellular carcinoma, Mol. Ther., 24, 755 Wang, 2020, m6A RNA methyltransferases METTL3/14 regulate immune responses to anti-PD-1 therapy, EMBO J., 39, 10.15252/embj.2020104514 Chen, 2022, METTL3 inhibits antitumor immunity by targeting m6A-BHLHE41-CXCL1/CXCR2 axis to promote colorectal cancer, Gastroenterology, 163, 891, 10.1053/j.gastro.2022.06.024 Zeng, 2022, Epigenetic activation of RBM15 promotes clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by regulating the m6A modification of CXCL11, Free Radic. Biol. Med., 184, 135, 10.1016/j.freeradbiomed.2022.03.031 Dong, 2021, ALKBH5 facilitates hypoxia-induced paraspeckle assembly and IL8 secretion to generate an immunosuppressive tumor microenvironment, Cancer Res, 81, 5876, 10.1158/0008-5472.CAN-21-1456 You, 2022, ALKBH5/MAP3K8 axis regulates PD-L1+ macrophage infiltration and promotes hepatocellular carcinoma progression, Int. J. Biol. Sci., 18, 5001, 10.7150/ijbs.70149 Jin, 2022, The m6A demethylase ALKBH5 promotes tumor progression by inhibiting RIG-I expression and interferon alpha production through the IKKε/TBK1/IRF3 pathway in head and neck squamous cell carcinoma, Mol. Cancer, 21, 97, 10.1186/s12943-022-01572-2 Qiu, 2022, Transcription elongation machinery is a druggable dependency and potentiates immunotherapy in glioblastoma stem CellsTargeting transcription machinery potentiates immunotherapy, Cancer Discov., 12, 502, 10.1158/2159-8290.CD-20-1848 Dunn, 1961, The occurence of 1-methyladenine in ribonucleic acid, Biochim. Biophys. Acta, 46, 198, 10.1016/0006-3002(61)90668-0 Helm, 1999, Watson− Crick Base-pair-disrupting methyl group (m1A9) is sufficient for cloverleaf folding of human mitochondrial tRNALys, Biochemistry, 38, 13338, 10.1021/bi991061g Sharma, 2013, Identification of a novel methyltransferase, Bmt2, responsible for the N-1-methyl-adenosine base modification of 25S rRNA in Saccharomyces cerevisiae, Nucleic Acids Res., 41, 5428, 10.1093/nar/gkt195 Dominissini, 2016, The dynamic N1-methyladenosine methylome in eukaryotic messenger RNA, Nature, 530, 441, 10.1038/nature16998 Li, 2016, Transcriptome-wide mapping reveals reversible and dynamic N1-methyladenosine methylome, Nat. Chem. Biol., 12, 311, 10.1038/nchembio.2040 Yao, 2022, M1ARegpred: epitranscriptome target prediction of N1-methyladenosine (m1A) regulators based on sequencing features and genomic features, Front. Biosci., 27, 269, 10.31083/j.fbl2709269 Chen, 2016, RAMPred: identifying the N1-methyladenosine sites in eukaryotic transcriptomes, Sci. Rep., 6, 31080, 10.1038/srep31080 Ozanick, 2005, The bipartite structure of the tRNA m1A58 methyltransferase from S. cerevisiae is conserved in humans, Rna, 11, 1281, 10.1261/rna.5040605 Chujo, 2012, Trmt61B is a methyltransferase responsible for 1-methyladenosine at position 58 of human mitochondrial tRNAs, Rna, 18, 2269, 10.1261/rna.035600.112 Vilardo, 2012, A subcomplex of human mitochondrial RNase P is a bifunctional methyltransferase—extensive moonlighting in mitochondrial tRNA biogenesis, Nucleic Acids Res., 40, 11583, 10.1093/nar/gks910 Safra, 2017, The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution, Nature, 551, 251, 10.1038/nature24456 Waku, 2016, NML-mediated rRNA base methylation links ribosomal subunit formation to cell proliferation in a p53-dependent manner, J. Cell Sci., 129, 2382 Dai, 2018, Identification of YTH Domain-containing proteins as the readers for N 1-Methyladenosine in RNA, Anal. Chem., 90, 6380, 10.1021/acs.analchem.8b01703 Liu, 2016, ALKBH1-mediated tRNA demethylation regulates translation, Cell, 167, 1897, 10.1016/j.cell.2016.11.045 Chen, 2019, Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs, Nucleic Acids Res., 47, 2533, 10.1093/nar/gky1250 Zhang, 2021, ALKBH7-mediated demethylation regulates mitochondrial polycistronic RNA processing, Nat. Cell Biol., 23, 684, 10.1038/s41556-021-00709-7 Wei, 2018, Differential m6A, m6Am, and m1A demethylation mediated by FTO in the cell nucleus and cytoplasm, Mol. Cell, 71, 973, 10.1016/j.molcel.2018.08.011 Agris, 1996, The importance of being modified: roles of modified nucleosides and Mg2+ in RNA structure and function, Prog. Nucleic Acid Res. Mol. Biol., 53, 79, 10.1016/S0079-6603(08)60143-9 Zhao, 2019, m1A regulated genes modulate PI3K/AKT/mTOR and ErbB pathways in gastrointestinal cancer, Transl. Oncol., 12, 1323, 10.1016/j.tranon.2019.06.007 Woo, 2019, Human ALKBH3-induced m1A demethylation increases the CSF-1 mRNA stability in breast and ovarian cancer cells, Biochim. Biophys. Acta. Gene Regul. Mech., 1862, 35, 10.1016/j.bbagrm.2018.10.008 Wu, 2022, RNA m 1 A methylation regulates glycolysis of cancer cells through modulating ATP5D, Proc. Natl. Acad. Sci. USA, 119, 10.1073/pnas.2119038119 Seo, 2019, YTHDF2 recognition of N1-methyladenosine (m1A)-modified RNA is associated with transcript destabilization, ACS Chem. Biol., 15, 132, 10.1021/acschembio.9b00655 Zheng, 2020, Cytoplasmic m1A reader YTHDF3 inhibits trophoblast invasion by downregulation of m1A-methylated IGF1R, Cell Discov., 6, 12, 10.1038/s41421-020-0144-4 Wang, 2021, N1-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism, Nat. Commun., 12, 6314, 10.1038/s41467-021-26718-6 Liu, 2022, tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis, Nat. Immunol., 23, 1433, 10.1038/s41590-022-01301-3 Wu, 2022, N1-Methyladenosine (m1A) regulation associated with the pathogenesis of abdominal aortic aneurysm through YTHDF3 modulating macrophage polarization, Front. Cardiovasc. Med., 9, 883155, 10.3389/fcvm.2022.883155 Gao, 2021, The Impact of m1A methylation modification patterns on tumor immune microenvironment and prognosis in oral squamous cell carcinoma, Int. J. Mol. Sci., 22, 10.3390/ijms221910302 Gao, 2021, Integrated analyses of m1A regulator-mediated modification patterns in tumor microenvironment-infiltrating immune cells in colon cancer, OncoImmunology, 10, 10.1080/2162402X.2021.1936758 Zhao, 2022, A novel m1A-score model correlated with the immune microenvironment predicts prognosis in hepatocellular carcinoma, Front. Immunol., 13, 805967, 10.3389/fimmu.2022.805967 Liu, 2021, Comprehensive of N1-methyladenosine modifications patterns and immunological characteristics in ovarian cancer, Front. Immunol., 12, 746647, 10.3389/fimmu.2021.746647 Bao, 2022, Comprehensive analysis of immune profiles and clinical significance of m1A regulators in lung adenocarcinoma, Front. Oncol., 2269 Chen, 2021, Dynamic transcriptomic m5C and its regulatory role in RNA processing, Wiley Interdiscip. Rev. RNA, 12, e1639, 10.1002/wrna.1639 Chen, 2022, Predicting RNA 5-methylcytosine sites by using essential sequence features and distributions, BioMed Res. Int., 2022, 4035462 Sharma, 2013, Yeast Nop2 and Rcm1 methylate C2870 and C2278 of the 25S rRNA, respectively, Nucleic Acids Res., 41, 9062, 10.1093/nar/gkt679 Hussain, 2013, NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs, Cell Rep., 4, 255, 10.1016/j.celrep.2013.06.029 Nakano, 2016, NSUN3 methylase initiates 5-formylcytidine biogenesis in human mitochondrial tRNAMet, Nat. Chem. Biol., 12, 546, 10.1038/nchembio.2099 Metodiev, 2014, NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly, PLoS Genet., 10, 10.1371/journal.pgen.1004110 Haag, 2015, NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs, Rna, 21, 1532, 10.1261/rna.051524.115 Goll, 2006, Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2, Science, 311, 395, 10.1126/science.1120976 Yang, 2017, 5-methylcytosine promotes mRNA export—NSUN2 as the methyltransferase and ALYREF as an m5C reader, Cell Res., 27, 606, 10.1038/cr.2017.55 Selmi, 2021, Sequence-and structure-specific cytosine-5 mRNA methylation by NSUN6, Nucleic Acids Res., 49, 1006, 10.1093/nar/gkaa1193 Yang, 2019, RNA 5-methylcytosine facilitates the maternal-to-zygotic transition by preventing maternal mRNA decay, Mol. Cell, 75, 1188, 10.1016/j.molcel.2019.06.033 Zou, 2020, Drosophila YBX1 homolog YPS promotes ovarian germ line stem cell development by preferentially recognizing 5-methylcytosine RNAs, Proc. Natl. Acad. Sci. USA, 117, 3603, 10.1073/pnas.1910862117 Dai, 2019, YTHDF2 binds to 5-methylcytosine in RNA and modulates the maturation of ribosomal RNA, Anal. Chem., 92, 1346, 10.1021/acs.analchem.9b04505 Fu, 2014, Tet-mediated formation of 5-hydroxymethylcytosine in RNA, J. Am. Chem. Soc., 136, 11582, 10.1021/ja505305z Heissenberger, 2019, Loss of the ribosomal RNA methyltransferase NSUN5 impairs global protein synthesis and normal growth, Nucleic Acids Res., 47, 11807, 10.1093/nar/gkz1043 Chen, 1993, 5-Methylcytidine is required for cooperative binding of magnesium (2+) and a conformational transition at the anticodon stem-loop of yeast phenylalanine tRNA, Biochemistry, 32, 10249, 10.1021/bi00089a047 Chan, 2012, Reprogramming of tRNA modifications controls the oxidative stress response by codon-biased translation of proteins, Nat. Commun., 3, 937, 10.1038/ncomms1938 Blanco, 2014, Aberrant methylation of t RNA s links cellular stress to neuro-developmental disorders, EMBO J, 33, 2020, 10.15252/embj.201489282 Shen, 2021, TET-mediated 5-methylcytosine oxidation in tRNA promotes translation, J. Biol. Chem., 296, 100087, 10.1074/jbc.RA120.014226 Wang, 2021, The role of the HIF-1α/ALYREF/PKM2 axis in glycolysis and tumorigenesis of bladder cancer, Cancer Commun., 41, 560, 10.1002/cac2.12158 Chen, 2019, 5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs, Nat. Cell Biol., 21, 978, 10.1038/s41556-019-0361-y Wang, 2017, Homocysteine upregulates interleukin-17A expression via NSun2-mediated RNA methylation in T lymphocytes, Biochem. Biophys. Res. Commun., 493, 94, 10.1016/j.bbrc.2017.09.069 Luo, 2016, NSun2 deficiency protects endothelium from inflammation via mRNA methylation of ICAM-1, Circ. Res., 118, 944, 10.1161/CIRCRESAHA.115.307674 Li, 2017, NSUN2-mediated m5C methylation and METTL3/METTL14-mediated m6A methylation cooperatively enhance p21 translation, J. Cell. Biochem., 118, 2587, 10.1002/jcb.25957 Tang, 2015, NSun2 delays replicative senescence by repressing p27 (KIP1) translation and elevating CDK1 translation, Aging (Albany NY), 7, 1143, 10.18632/aging.100860 Blanco, 2011, The RNA–methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate, PLoS Genet, 7, 10.1371/journal.pgen.1002403 Flores, 2017, Cytosine-5 RNA methylation regulates neural stem cell differentiation and motility, Stem Cell Rep., 8, 112, 10.1016/j.stemcr.2016.11.014 Cai, 2016, RNA methyltransferase NSUN2 promotes stress-induced HUVEC senescence, Oncotarget, 7, 19099, 10.18632/oncotarget.8087 Hu, 2021, NSUN2 modified by SUMO-2/3 promotes gastric cancer progression and regulates mRNA m5C methylation, Cell Death Dis., 12, 842, 10.1038/s41419-021-04127-3 Sun, 2020, Aberrant NSUN2-mediated m5C modification of H19 lncRNA is associated with poor differentiation of hepatocellular carcinoma, Oncogene, 39, 6906, 10.1038/s41388-020-01475-w Su, 2021, NSUN2-mediated RNA 5-methylcytosine promotes esophageal squamous cell carcinoma progression via LIN28B-dependent GRB2 mRNA stabilization, Oncogene, 40, 5814, 10.1038/s41388-021-01978-0 Li, 2019, Ten-eleven translocation (TET) enzymes modulate the activation of dendritic cells in allergic rhinitis, Front. Immunol., 10, 2271, 10.3389/fimmu.2019.02271 Schoeler, 2019, TET enzymes control antibody production and shape the mutational landscape in germinal centre B cells, FEBS J., 286, 3566, 10.1111/febs.14934 Yue, 2019, Loss of TET2 and TET3 in regulatory T cells unleashes effector function, Nat. Commun., 10, 2011, 10.1038/s41467-019-09541-y Tao, 2019, Targeting the YB-1/PD-L1 Axis to enhance chemotherapy and antitumor immunityYB-1 promotes tumor immune evasion, Cancer Immunol. Res., 7, 1135, 10.1158/2326-6066.CIR-18-0648 Huang, 2021, Prognostic significance and tumor immune microenvironment heterogenicity of m5C RNA methylation regulators in triple-negative breast cancer, Front. Cell Dev. Biol., 9, 657547, 10.3389/fcell.2021.657547 Tong, 2022, NSUN2 promotes tumor progression and regulates immune infiltration in nasopharyngeal carcinoma, Front. Oncol., 12, 788801, 10.3389/fonc.2022.788801 Pan, 2021, m5C RNA methylation regulators predict prognosis and regulate the immune microenvironment in lung squamous cell carcinoma, Front. Oncol., 11, 10.3389/fonc.2021.657466 Xue, 2020, Gene signatures of m5C regulators may predict prognoses of patients with head and neck squamous cell carcinoma, Am. J. Transl. Res., 12, 6841 Li, 2021, m5C regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in papillary thyroid carcinoma, Front. Oncol., 11 Gao, 2021, The RNA methylation modification 5-Methylcytosine impacts immunity characteristics, prognosis and progression of Oral squamous cell carcinoma by bioinformatics analysis, Front. Bioeng. Biotechnol., 9, 760724, 10.3389/fbioe.2021.760724 Xu, 2021, Integrative 5-methylcytosine modification immunologically reprograms tumor microenvironment characterizations and phenotypes of clear cell renal cell carcinoma, Front. Cell Dev. Biol., 9, 772436, 10.3389/fcell.2021.772436 Yu, 2022, Comprehensive analysis of m5C methylation regulatory genes and tumor microenvironment in prostate cancer, Front. Immunol., 13, 914577, 10.3389/fimmu.2022.914577 Boccaletto, 2022, MODOMICS: a database of RNA modification pathways. 2021 update, Nucleic Acids Res, 50, D231, 10.1093/nar/gkab1083 Cui, 2022, RNA modifications: importance in immune cell biology and related diseases, Signal Transduct. Target. Ther., 7, 334, 10.1038/s41392-022-01175-9 Wiener, 2021, The epitranscriptome beyond m6A, Nat. Rev. Genet., 22, 119, 10.1038/s41576-020-00295-8 Delaunay, 2022, Mitochondrial RNA modifications shape metabolic plasticity in metastasis, Nature, 607, 593, 10.1038/s41586-022-04898-5 Nakahama, 2020, Adenosine-to-inosine RNA editing in the immune system: friend or foe?, Cell. Mol. Life Sci., 77, 2931, 10.1007/s00018-020-03466-2 You, 2023, 6-Thioguanine incorporates into RNA and induces adenosine-to-inosine editing in acute lymphoblastic leukemia cells, Chinese Chem. Lett., 34, 10.1016/j.cclet.2022.01.074 Ishizuka, 2019, Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade, Nature, 565, 43, 10.1038/s41586-018-0768-9 Zeng, 2023, Eliminating METTL1-mediated accumulation of PMN-MDSCs prevents HCC recurrence after radiofrequency ablation, Hepatology, 77, 1122, 10.1002/hep.32585 Zhang, 2019, Transcriptome-wide mapping of internal N7-methylguanosine methylome in mammalian mRNA, Mol. Cell, 74, 1304, 10.1016/j.molcel.2019.03.036 Carlile, 2014, Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells, Nature, 515, 143, 10.1038/nature13802 Xiang, 2018, N6-Methyladenosines modulate A-to-I RNA editing, Mol. Cell, 69, 126, 10.1016/j.molcel.2017.12.006 Boo, 2022, m1A and m6A modifications function cooperatively to facilitate rapid mRNA degradation, Cell Rep., 40, 10.1016/j.celrep.2022.111317 Ontiveros, 2020, Coordination of mRNA and tRNA methylations by TRMT10A, Proc. Natl. Acad. Sci. USA, 117, 7782, 10.1073/pnas.1913448117 Zhao, 2021, The crosstalk between m6A RNA methylation and other epigenetic regulators: a novel perspective in epigenetic remodeling, Theranostics, 11, 4549, 10.7150/thno.54967 Wang, 2020, METTL3-mediated m6A modification of HDGF mRNA promotes gastric cancer progression and has prognostic significance, Gut, 69, 1193, 10.1136/gutjnl-2019-319639 Huang, 2019, Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally, Nature, 567, 414, 10.1038/s41586-019-1016-7 Deng, 2022, RNA m6A regulates transcription via DNA demethylation and chromatin accessibility, Nat. Genet., 54, 1427, 10.1038/s41588-022-01173-1 Uddin, 2021, The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis, Mol. Cancer, 20, 61, 10.1186/s12943-021-01356-0 Bao, 2023, RM2Target: a comprehensive database for targets of writers, erasers and readers of RNA modifications, Nucleic Acids Res., 51, D269, 10.1093/nar/gkac945 Tang, 2021, m6A-Atlas: a comprehensive knowledgebase for unraveling the N 6-methyladenosine (m6A) epitranscriptome, Nucleic Acids Res., 49, D134, 10.1093/nar/gkaa692 Liu, 2020, REPIC: a database for exploring the N 6-methyladenosine methylome, Genome Biol., 21, 100, 10.1186/s13059-020-02012-4 Zhang, 2023, DirectRMDB: a database of post-transcriptional RNA modifications unveiled from direct RNA sequencing technology, Nucleic Acids Res., 51, D106, 10.1093/nar/gkac1061 Luo, 2021, RMVar: an updated database of functional variants involved in RNA modifications, Nucleic Acids Res., 49, D1405, 10.1093/nar/gkaa811 Song, 2023, RMDisease V2. 0: an updated database of genetic variants that affect RNA modifications with disease and trait implication, Nucleic Acids Res., 51, D1388, 10.1093/nar/gkac750 Xuan, 2018, RMBase v2. 0: deciphering the map of RNA modifications from epitranscriptome sequencing data, Nucleic Acids Res., 46, D327, 10.1093/nar/gkx934 Ma, 2022, m5C-Atlas: a comprehensive database for decoding and annotating the 5-methylcytosine (m5C) epitranscriptome, Nucleic Acids Res., 50, D196, 10.1093/nar/gkab1075 Chen, 2018, iRNA-3typeA: identifying three types of modification at RNA’s adenosine sites, Mol. Ther. Acids, 11, 468, 10.1016/j.omtn.2018.03.012 Lv, 2020, Evaluation of different computational methods on 5-methylcytosine sites identification, Brief. Bioinform., 21, 982, 10.1093/bib/bbz048 Li, 2018, RNAm5Cfinder: a web-server for predicting RNA 5-methylcytosine (m5C) sites based on random forest, Sci. Rep., 8, 10.1038/s41598-018-35502-4 Zhang, 2018, Accurate RNA 5-methylcytosine site prediction based on heuristic physical-chemical properties reduction and classifier ensemble, Anal. Biochem., 550, 41, 10.1016/j.ab.2018.03.027 Jiang, 2022, m6AmPred: identifying RNA N6, 2′-O-dimethyladenosine (m6Am) sites based on sequence-derived information, Methods, 203, 328, 10.1016/j.ymeth.2021.01.007 Song, 2021, Attention-based multi-label neural networks for integrated prediction and interpretation of twelve widely occurring RNA modifications, Nat. Commun., 12, 4011, 10.1038/s41467-021-24313-3