Methylation modifications in tRNA and associated disorders: Current research and potential therapeutic targets

Zhijing Wu , Ruixin Zhou , Baizao Li , Mingyu Cao , Wenlong Wang , Xinying Li

Cell Proliferation ›› 2024, Vol. 57 ›› Issue (9) : e13692

PDF
Cell Proliferation ›› 2024, Vol. 57 ›› Issue (9) : e13692 DOI: 10.1111/cpr.13692
REVIEW

Methylation modifications in tRNA and associated disorders: Current research and potential therapeutic targets

Author information +
History +
PDF

Abstract

High-throughput sequencing has sparked increased research interest in RNA modifications, particularly tRNA methylation, and its connection to various diseases. However, the precise mechanisms underpinning the development of these diseases remain largely elusive. This review sheds light on the roles of several tRNA methylations (m1A, m3C, m5C, m1G, m2G, m7G, m5U, and Nm) in diverse biological functions, including metabolic processing, stability, protein interactions, and mitochondrial activities. It further outlines diseases linked to aberrant tRNA modifications, related enzymes, and potential underlying mechanisms. Moreover, disruptions in tRNA regulation and abnormalities in tRNA-derived small RNAs (tsRNAs) contribute to disease pathogenesis, highlighting their potential as biomarkers for disease diagnosis. The review also delves into the exploration of drugs development targeting tRNA methylation enzymes, emphasizing the therapeutic prospects of modulating these processes. Continued research is imperative for a comprehensive comprehension and integration of these molecular mechanisms in disease diagnosis and treatment.

Cite this article

Download citation ▾
Zhijing Wu, Ruixin Zhou, Baizao Li, Mingyu Cao, Wenlong Wang, Xinying Li. Methylation modifications in tRNA and associated disorders: Current research and potential therapeutic targets. Cell Proliferation, 2024, 57(9): e13692 DOI:10.1111/cpr.13692

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

BarbieriI, Kouzarides T. Role of RNA modifications in cancer. Nat Rev Cancer. 2020; 20(6):303-322.

[2]

ChenRZ, Pettersson U, BeardC, Jackson-GrusbyL, Jaenisch R. DNA hypomethylation leads to elevated mutation rates. Nature. 1998; 395(6697):89-93.

[3]

GuoH, VuilleJA, WittnerBS, et al. DNA hypomethylation silences anti-tumor immune genes in early prostate cancer and CTCs. Cell. 2023; 186(13):2765-2782.e28.

[4]

PichotF, HoggMC, MarchandV, et al. Quantification of substoichiometric modification reveals global tsRNA hypomodification, preferences for angiogenin-mediated tRNA cleavage, and idiosyncratic epitranscriptomes of human neuronal cell-lines. Comput Struct Biotechnol J. 2023; 21:401-417.

[5]

MehboobMZ, LangM. Structure, function, and pathology of protein O-glucosyltransferases. Cell Death Dis. 2021; 12(1):71.

[6]

LorenzC, Lünse CE, MörlM. tRNA modifications: impact on structure and thermal adaptation. Biomolecules. 2017; 7(2):1-29.

[7]

WangY, TaoEW, TanJ, GaoQY, ChenYX, Fang JY. tRNA modifications: insights into their role in human cancers. Trends Cell Biol. 2023; 33:1035-1048.

[8]

BoccalettoP, Stefaniak F, RayA, et al. MODOMICS: a database of RNA modification pathways. 2021 update. Nucleic Acids Res. 2022; 50(D1):D231-d235.

[9]

NauF. The methylation of tRNA. Biochimie. 1976; 58(6):629-645.

[10]

SuzukiT. The expanding world of tRNA modifications and their disease relevance. Nat Rev Mol Cell Biol. 2021; 22(6):375-392.

[11]

OrellanaEA, SiegalE, GregoryRI. tRNA dysregulation and disease. Nat Rev Genet. 2022; 23(11):651-664.

[12]

HuangH, LiH, PanR, WangS, LiuX. tRNA modifications and their potential roles in pancreatic cancer. Arch Biochem Biophys. 2021; 714:109083.

[13]

BianM, HuangS, YuD, ZhouZ. tRNA metabolism and lung cancer: beyond translation. Front Mol Biosci. 2021; 8:659388.

[14]

EndresL, Fasullo M, RoseR. tRNA modification and cancer: potential for therapeutic prevention and intervention. Future Med Chem. 2019; 11(8):885-900.

[15]

LiJ, ZhangH, WangH. N(1)-methyladenosine modification in cancer biology: current status and future perspectives. Comput Struct Biotechnol J. 2022; 20:6578-6585.

[16]

ChujoT, SuzukiT. Trmt61B is a methyltransferase responsible for 1-methyladenosine at position 58 of human mitochondrial tRNAs. RNA. 2012; 18(12):2269-2276.

[17]

KrishnamohanA, Dodbele S, JackmanJE. Insights into catalytic and tRNA recognition mechanism of the dual-specific tRNA methyltransferase from Thermococcus kodakarensis. Genes (Basel). 2019; 10(2):1-14.

[18]

HowellNW, JoraM, JepsonBF, Limbach PA, JackmanJE. Distinct substrate specificities of the human tRNA methyltransferases TRMT10A and TRMT10B. RNA. 2019; 25(10):1366-1376.

[19]

WeiJ, LiuF, LuZ, et al. Differential m(6)A, m(6)A(m), and m(1)A demethylation mediated by FTO in the cell nucleus and cytoplasm. Mol Cell. 2018; 71(6):973-985.e5.

[20]

RashadS, HanX, SatoK, et al. The stress specific impact of ALKBH1 on tRNA cleavage and tiRNA generation. RNA Biol. 2020; 17(8):1092-1103.

[21]

WagnerA, Hofmeister O, RollandSG, et al. Mitochondrial Alkbh1 localizes to mtRNA granules and its knockdown induces the mitochondrial UPR in humans and C. elegans. J Cell Sci. 2019; 132(19):1-12.

[22]

ZhangLS, XiongQP, Peña PerezS, et al. ALKBH7-mediated demethylation regulates mitochondrial polycistronic RNA processing. Nat Cell Biol. 2021; 23(7):684-691.

[23]

OuglandR, RognesT, KlunglandA, Larsen E. Non-homologous functions of the AlkB homologs. J Mol Cell Biol. 2015; 7(6):494-504.

[24]

JiaG, FuY, ZhaoX, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol. 2011; 7(12):885-887.

[25]

DaiX, WangT, GonzalezG, Wang Y. Identification of YTH domain-containing proteins as the readers for N1-Methyladenosine in RNA. Anal Chem. 2018; 90(11):6380-6384.

[26]

ScheitlCPM, Mieczkowski M, SchindelinH, HöbartnerC. Structure and mechanism of the methyltransferase ribozyme MTR1. Nat Chem Biol. 2022; 18(5):547-555.

[27]

SuZ, Monshaugen I, WilsonB, et al. TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer. Nat Commun. 2022; 13(1):2165.

[28]

WangY, WangJ, LiX, et al. N(1)-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism. Nat Commun. 2021; 12(1):6314.

[29]

MacariF, el-houfi Y, BoldinaG, et al. TRM6/61 connects PKCα with translational control through tRNAi(Met) stabilization: impact on tumorigenesis. Oncogene. 2016; 35(14):1785-1796.

[30]

ChenZ, QiM, ShenB, et al. Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs. Nucleic Acids Res. 2019; 47(5):2533-2545.

[31]

LiL, TanH, ZhouJ, Hu F. Predicting response of immunotherapy and targeted therapy and prognosis characteristics for renal clear cell carcinoma based on m1A methylation regulators. Sci Rep. 2023; 13(1):12645.

[32]

m1A tRNA modification facilitates rapid T cell proliferation. Nat Immunol. 2022; 23(10):1408-1409.

[33]

LiuY, ZhouJ, LiX, et al. tRNA-m(1)a modification promotes T cell expansion via efficient MYC protein synthesis. Nat Immunol. 2022; 23(10):1433-1444.

[34]

ClarkKD, LeeC, GilletteR, Sweedler JV. Characterization of neuronal RNA modifications during non-associative learning in Aplysia reveals key roles for tRNAs in behavioral sensitization. ACS Cent Sci. 2021; 7(7):1183-1190.

[35]

RichterU, EvansME, ClarkWC, et al. RNA modification landscape of the human mitochondrial tRNA(Lys) regulates protein synthesis. Nat Commun. 2018; 9(1):3966.

[36]

ShafikAM, ZhouH, LimJ, Dickinson B, JinP. Dysregulated mitochondrial and cytosolic tRNA m1A methylation in Alzheimer’s disease. Hum Mol Genet. 2022; 31(10):1673-1680.

[37]

FukudaH, ChujoT, WeiFY, et al. Cooperative methylation of human tRNA3Lys at positions A58 and U54 drives the early and late steps of HIV-1 replication. Nucleic Acids Res. 2021; 49(20):11855-11867.

[38]

ŠimonováA, SvojanovskáB, Trylčová J, et al. LC/MS analysis and deep sequencing reveal the accurate RNA composition in the HIV-1 virion. Sci Rep. 2019; 9(1):8697.

[39]

ZhangHX, YuD, SunJF, et al. An integrated approach to evaluate acetamiprid-induced oxidative damage to tRNA in human cells based on oxidized nucleotide and tRNA profiling. Environ Int. 2023; 178:108038.

[40]

LeeHK, LeeBR, LeeTJ, et al. Differential release of extracellular vesicle tRNA from oxidative stressed renal cells and ischemic kidneys. Sci Rep. 2022; 12(1):1646.

[41]

EvkeS, LinQ, MelendezJA, Begley TJ. Epitranscriptomic reprogramming is required to prevent stress and damage from acetaminophen. Genes (Basel). 2022; 13(3):1-23.

[42]

ArzumanianVA, Dolgalev GV, KurbatovIY, KiselevaOI, Poverennaya EV. Epitranscriptome: review of top 25 Most-studied RNA modifications. Int J Mol Sci. 2022; 23(22):1-23.

[43]

BohnsackKE, Kleiber N, Lemus-DiazN, BohnsackMT. Roles and dynamics of 3-methylcytidine in cellular RNAs. Trends Biochem Sci. 2022; 47(7):596-608.

[44]

XuL, LiuX, ShengN, et al. Three distinct 3-methylcytidine (m(3)C) methyltransferases modify tRNA and mRNA in mice and humans. J Biol Chem. 2017; 292(35):14695-14703.

[45]

MaoXL, LiZH, HuangMH, et al. Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6. Nucleic Acids Res. 2021; 49(14):8309-8323.

[46]

LentiniJM, AlsaifHS, FaqeihE, Alkuraya FS, FuD. DALRD3 encodes a protein mutated in epileptic encephalopathy that targets arginine tRNAs for 3-methylcytosine modification. Nat Commun. 2020; 11(1):2510.

[47]

LiS, ZhouH, LiaoS, et al. Structural basis for METTL6-mediated m3C RNA methylation. Biochem Biophys Res Commun. 2022; 589:159-164.

[48]

SchöllerE, MarksJ, MarchandV, et al. Balancing of mitochondrial translation through METTL8-mediated m(3)C modification of mitochondrial tRNAs. Mol Cell. 2021; 81(23):4810-4825.e12.

[49]

KleiberN, Lemus-Diaz N, StillerC, et al. The RNA methyltransferase METTL8 installs m(3)C(32) in mitochondrial tRNAs(Thr/ser(UCN)) to optimise tRNA structure and mitochondrial translation. Nat Commun. 2022; 13(1):209.

[50]

ChenR, ZhouJ, LiuL, MaoXL, ZhouX, Xie W. Crystal structure of human METTL6, the m(3)C methyltransferase. Commun Biol. 2021; 4(1):1361.

[51]

LentiniJM, Bargabos R, ChenC, FuD. Methyltransferase METTL8 is required for 3-methylcytosine modification in human mitochondrial tRNAs. J Biol Chem. 2022; 298(4):101788.

[52]

WangS, LiH, LiuJ, et al. Integrative analysis of m3C associated genes reveals METTL2A as a potential oncogene in breast cancer. J Transl Med. 2022; 20(1):476.

[53]

IgnatovaVV, KaiserS, HoJSY, et al. METTL6 is a tRNA m(3)C methyltransferase that regulates pluripotency and tumor cell growth. Sci Adv. 2020; 6(35):eaaz4551.

[54]

BolatkanA, AsadaK, KanekoS, et al. Downregulation of METTL6 mitigates cell progression, migration, invasion and adhesion in hepatocellular carcinoma by inhibiting cell adhesion molecules. Int J Oncol. 2022; 60(1):1-13.

[55]

TanXL, MoyerAM, FridleyBL, et al. Genetic variation predicting cisplatin cytotoxicity associated with overall survival in lung cancer patients receiving platinum-based chemotherapy. Clin Cancer Res. 2011; 17(17):5801-5811.

[56]

YeonSY, JoYS, ChoiEJ, Kim MS, YooNJ, LeeSH. Frameshift mutations in repeat sequences of ANK3, HACD4, TCP10L, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8 and METTL16 genes in colon cancers. Pathol Oncol Res. 2018; 24(3):617-622.

[57]

TangM, LiY, LuoX, et al. Identification of biomarkers related to CD8(+) T cell infiltration with gene Co-expression network in lung squamous cell carcinoma. Front Cell Dev Biol. 2021; 9:606106.

[58]

ZhangF, YoonK, ZhangDY, Kim NS, MingGL, SongH. Epitranscriptomic regulation of cortical neurogenesis via Mettl8-dependent mitochondrial tRNA m(3)C modification. Cell Stem Cell. 2023; 30(3):300-311.e11.

[59]

SquiresJE, PatelHR, NouschM, et al. Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Res. 2012; 40(11):5023-5033.

[60]

GollMG, Kirpekar F, MaggertKA, et al. Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science. 2006; 311(5759):395-398.

[61]

LongT, LiJ, LiH, et al. Sequence-specific and shape-selective RNA recognition by the human RNA 5-Methylcytosine methyltransferase NSun6. J Biol Chem. 2016; 291(46):24293-24303.

[62]

KingMY, RedmanKL. RNA methyltransferases utilize two cysteine residues in the formation of 5-methylcytosine. Biochemistry. 2002; 41(37):11218-11225.

[63]

BohnsackKE, Höbartner C, BohnsackMT. Eukaryotic 5-methylcytosine (m5C) RNA methyltransferases: mechanisms, cellular functions, and links to disease. Genes (Basel). 2019; 10(2):1-17.

[64]

AuxilienS, Guérineau V, Szweykowska-Kulińska Z, Golinelli-PimpaneauB. The human tRNA m (5) C methyltransferase Misu is multisite-specific. RNA Biol. 2012; 9(11):1331-1338.

[65]

BrzezichaB, Schmidt M, MakałowskaI, JarmołowskiA, PieńkowskaJ, Szweykowska-Kulińska Z. Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the pre-tRNA leu (CAA). Nucleic Acids Res. 2006; 34(20):6034-6043.

[66]

van HauteL, LeeSY, McCannBJ, et al. NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs. Nucleic Acids Res. 2019; 47(16):8720-8733.

[67]

NakanoS, SuzukiT, KawaradaL, Iwata H, AsanoK, SuzukiT. NSUN3 methylase initiates 5-formylcytidine biogenesis in human mitochondrial tRNA(met). Nat Chem Biol. 2016; 12(7):546-551.

[68]

HaagS, WardaAS, KretschmerJ, Günnigmann MA, HöbartnerC, BohnsackMT. NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs. RNA. 2015; 21(9):1532-1543.

[69]

LiuRJ, LongT, LiJ, LiH, WangED. Structural basis for substrate binding and catalytic mechanism of a human RNA:m5C methyltransferase NSun6. Nucleic Acids Res. 2017; 45(11):6684-6697.

[70]

HuangZX, LiJ, XiongQP, Li H, WangED, LiuRJ. Position 34 of tRNA is a discriminative element for m5C38 modification by human DNMT2. Nucleic Acids Res. 2021; 49(22):13045-13061.

[71]

HuberSM, van Delft P, TanpureA, MiskaEA, Balasubramanian S. 2’-O-Methyl-5-hydroxymethylcytidine: a second oxidative derivative of 5-methylcytidine in RNA. J Am Chem Soc. 2017; 139(5):1766-1769.

[72]

ArguelloAE, LiA, SunX, EggertTW, MairhoferE, Kleiner RE. Reactivity-dependent profiling of RNA 5-methylcytidine dioxygenases. Nat Commun. 2022; 13(1):4176.

[73]

HeC, BozlerJ, JanssenKA, et al. TET2 chemically modifies tRNAs and regulates tRNA fragment levels. Nat Struct Mol Biol. 2021; 28(1):62-70.

[74]

KawaradaL, SuzukiT, OhiraT, Hirata S, MiyauchiK, SuzukiT. ALKBH1 is an RNA dioxygenase responsible for cytoplasmic and mitochondrial tRNA modifications. Nucleic Acids Res. 2017; 45(12):7401-7415.

[75]

TuortoF, Liebers R, MuschT, et al. RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nat Struct Mol Biol. 2012; 19(9):900-905.

[76]

ChenY, Sierzputowska-Gracz H, GuentherR, EverettK, AgrisPF. 5-methylcytidine is required for cooperative binding of Mg2+ and a conformational transition at the anticodon stem-loop of yeast phenylalanine tRNA. Biochemistry. 1993; 32(38):10249-10253.

[77]

XuY, MacKerell AD Jr, NilssonL. Structural effects of modified ribonucleotides and magnesium in transfer RNAs. Bioorg Med Chem. 2016; 24(20):4826-4834.

[78]

VäreVY, Eruysal ER, NarendranA, et al. Chemical and conformational diversity of modified nucleosides affects tRNA structure and function. Biomolecules. 2017; 7(1):1-32.

[79]

HaagS, SloanKE, RanjanN, et al. NSUN3 and ABH1 modify the wobble position of mt-tRNAMet to expand codon recognition in mitochondrial translation. EMBO J. 2016; 35(19):2104-2119.

[80]

TuortoF, HerbstF, AlerasoolN, et al. The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis. EMBO J. 2015; 34(18):2350-2362.

[81]

ShanmugamR, FiererJ, KaiserS, Helm M, JurkowskiTP, JeltschA. Cytosine methylation of tRNA-Asp by DNMT2 has a role in translation of proteins containing poly-Asp sequences. Cell Discov. 2015; 1:15010.

[82]

OkamotoM, HirataS, SatoS, et al. Frequent increased gene copy number and high protein expression of tRNA (cytosine-5-)-methyltransferase (NSUN2) in human cancers. DNA Cell Biol. 2012; 31(5):660-671.

[83]

ElhardtW, Shanmugam R, JurkowskiTP, JeltschA. Somatic cancer mutations in the DNMT2 tRNA methyltransferase alter its catalytic properties. Biochimie. 2015; 112:66-72.

[84]

LuL, ZhuG, ZengH, Xu Q, HolzmannK. High tRNA transferase NSUN2 gene expression is associated with poor prognosis in head and neck squamous carcinoma. Cancer Invest. 2018; 36(4):246-253.

[85]

LuL, Gaffney SG, CannataroVL, TownsendJ. Transfer RNA methyltransferase gene NSUN2 mRNA expression modifies the effect of T cell activation score on patient survival in head and neck squamous carcinoma. Oral Oncol. 2020; 101:104554.

[86]

DelaunayS, Pascual G, FengB, et al. Mitochondrial RNA modifications shape metabolic plasticity in metastasis. Nature. 2022; 607(7919):593-603.

[87]

OkamotoM, Fujiwara M, HoriM, et al. tRNA modifying enzymes, NSUN2 and METTL1, determine sensitivity to 5-fluorouracil in HeLa cells. PLoS Genet. 2014; 10(9):e1004639.

[88]

MartinezFJ, LeeJH, LeeJE, et al. Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome. J Med Genet. 2012; 49(6):380-385.

[89]

BlancoS, Dietmann S, FloresJV, et al. Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. EMBO J. 2014; 33(18):2020-2039.

[90]

FloresJV, Cordero-Espinoza L, Oeztuerk-WinderF, et al. Cytosine-5 RNA methylation regulates neural stem cell differentiation and motility. Stem Cell Rep. 2017; 8(1):112-124.

[91]

BlazeJ, Navickas A, PhillipsHL, et al. Neuronal Nsun2 deficiency produces tRNA epitranscriptomic alterations and proteomic shifts impacting synaptic signaling and behavior. Nat Commun. 2021; 12(1):4913.

[92]

YingS, LiP, WangJ, et al. tRF-Gln-CTG-026 ameliorates liver injury by alleviating global protein synthesis. Signal Transduct Target Ther. 2023; 8(1):144.

[93]

VilardoE, AmmanF, TothU, Kotter A, HelmM, RossmanithW. Functional characterization of the human tRNA methyltransferases TRMT10A and TRMT10B. Nucleic Acids Res. 2020; 48(11):6157-6169.

[94]

BruléH, Elliott M, RedlakM, ZehnerZE, HolmesWM. Isolation and characterization of the human tRNA-(N1G37) methyltransferase (TRM5) and comparison to the Escherichia coli TrmD protein. Biochemistry. 2004; 43(28):9243-9255.

[95]

ParisZ, Horáková E, RubioMAT, et al. The T. Brucei TRM5 methyltransferase plays an essential role in mitochondrial protein synthesis and function. RNA. 2013; 19(5):649-658.

[96]

CozenAE, Quartley E, HolmesAD, Hrabeta-RobinsonE, Phizicky EM, LoweTM. ARM-seq: AlkB-facilitated RNA methylation sequencing reveals a complex landscape of modified tRNA fragments. Nat Methods. 2015; 12(9):879-884.

[97]

OntiverosRJ, ShenH, StouteJ, et al. Coordination of mRNA and tRNA methylations by TRMT10A. Proc Natl Acad Sci U S A. 2020; 117(14):7782-7791.

[98]

ZhengG, QinY, ClarkWC, et al. Efficient and quantitative high-throughput tRNA sequencing. Nat Methods. 2015; 12(9):835-837.

[99]

IdaghdourY, Hodgkinson A. Integrated genomic analysis of mitochondrial RNA processing in human cancers. Genome Med. 2017; 9(1):36.

[100]

SuZ, Monshaugen I, KlunglandA, OuglandR, DuttaA. Characterization of novel small non-coding RNAs and their modifications in bladder cancer using an updated small RNA-seq workflow. Front Mol Biosci. 2022; 9:887686.

[101]

ChangQ, ChenP, YinJ, et al. Discovery and validation of bladder cancer related excreted nucleosides biomarkers by dilution approach in cell culture supernatant and urine using UHPLC-MS/MS. J Proteomics. 2023; 270:104737.

[102]

FangZ, HuY, HongX, et al. Simultaneous determination of methylated nucleosides by HILIC-MS/MS revealed their alterations in urine from breast cancer patients. Metabolites. 2022; 12(10):1-12.

[103]

MonoeY, Miyamoto S, JingushiK, et al. Hypoxia regulates tumour characteristic RNA modifications in ovarian cancers. FEBS J. 2022; 290:2085-2096.

[104]

ZhangHX, QinJF, SunJF, et al. Selective chemical labeling strategy for oligonucleotides determination: a first application to full-range profiling of transfer RNA modifications. Anal Chem. 2023; 95(2):686-694.

[105]

ZhaoQ, ZhangL, HeQ, et al. Targeting TRMT5 suppresses hepatocellular carcinoma progression via inhibiting the HIF-1α pathways. J Zhejiang Univ Sci B. 2023; 24(1):50-63.

[106]

CosentinoC, Toivonen S, Diaz VillamilE, et al. Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes. Nucleic Acids Res. 2018; 46(19):10302-10318.

[107]

DodsonTA, Nieuwoudt S, MorseCN, et al. Ribonucleosides from tRNA in hyperglycemic mammalian cells and diabetic murine cardiac models. Life Sci. 2023; 318:121462.

[108]

ZungA, KoriM, BurundukovE, Ben-Yosef T, TatoorY, GranotE. Homozygous deletion of TRMT10A as part of a contiguous gene deletion in a syndrome of failure to thrive, delayed puberty, intellectual disability and diabetes mellitus. Am J Med Genet A. 2015; 167(12):3167-3173.

[109]

YewTW, McCreight L, ColcloughK, EllardS, Pearson ER. tRNA methyltransferase homologue gene TRMT10A mutation in young adult-onset diabetes with intellectual disability, microcephaly and epilepsy. Diabet Med. 2016; 33(9):e21-e25.

[110]

SternE, Vivante A, BarelO, Levy-ShragaY. TRMT10A mutation in a child with diabetes, short stature, microcephaly and hypoplastic kidneys. J Clin Res Pediatr Endocrinol. 2022; 14(2):227-232.

[111]

RoyK, Satapathy AK, HouhtonJAL, et al. Congenital hyperinsulinemic hypoglycemia and hyperammonemia due to pathogenic variants in GLUD1. Indian J Pediatr. 2019; 86(11):1051-1053.

[112]

GillisD, Krishnamohan A, YaacovB, ShaagA, Jackman JE, ElpelegO. TRMT10A dysfunction is associated with abnormalities in glucose homeostasis, short stature and microcephaly. J Med Genet. 2014; 51(9):581-586.

[113]

BrenerA, Zeitlin L, WilnaiY, et al. Looking for the skeleton in the closet-rare genetic diagnoses in patients with diabetes and skeletal manifestations. Acta Diabetol. 2022; 59(5):711-719.

[114]

PowellCA, Kopajtich R, D’SouzaAR, et al. TRMT5 mutations cause a defect in post-transcriptional modification of mitochondrial tRNA associated with multiple respiratory-chain deficiencies. Am J Hum Genet. 2015; 97(2):319-328.

[115]

TarnopolskyMA, BradyL, TetreaultM. TRMT5 mutations are associated with features of complex hereditary spastic paraparesis. Neurology. 2017; 89(21):2210-2211.

[116]

Argente-EscrigH, Vílchez JJ, FrasquetM, et al. A novel TRMT5 mutation causes a complex inherited neuropathy syndrome: the role of nerve pathology in defining a demyelinating neuropathy. Neuropathol Appl Neurobiol. 2022; 48(5):e12817.

[117]

WuS, LiW, BaiZ, et al. Novel heterozygous compound TRMT5 mutations associated with combined oxidative phosphorylation deficiency 26 in a Chinese family: a case report. BMC Pediatr. 2022; 22(1):74.

[118]

WarasnheK, Özçay F, Aydin, ÖzgünG, Ceylaner S. A novel mutation in TRMT5 associated with idiopathic non-cirrhotic portal hypertension and hepatopulmonary syndrome: case report of two siblings. Clin Res Hepatol Gastroenterol. 2022; 46(8):101928.

[119]

ZhouM, XueL, ChenY, et al. A hypertension-associated mitochondrial DNA mutation introduces an m1G37 modification into tRNAMet, altering its structure and function. J Biol Chem. 2018; 293(4):1425-1438.

[120]

MengF, ZhouM, XiaoY, et al. A deafness-associated tRNA mutation caused pleiotropic effects on the m1G37 modification, processing, stability and aminoacylation of tRNAIle and mitochondrial translation. Nucleic Acids Res. 2021; 49(2):1075-1093.

[121]

SongH, ChenS, ZhangT, et al. Integrated strategies of diverse feature selection methods identify aging-based reliable gene signatures for ischemic cardiomyopathy. Front Mol Biosci. 2022; 9:805235.

[122]

BaviRS, KambleAD, KumbharNM, Kumbhar BV, SonawaneKD. Conformational preferences of modified nucleoside N(2)-methylguanosine (m(2)G) and its derivative N(2), N(2)-dimethylguanosine (m(2)(2)G) occur at 26th position (hinge region) in tRNA. Cell Biochem Biophys. 2011; 61(3):507-521.

[123]

XiongQ-P, LiJ, LiH, et al. Human TRMT1 catalyzes m2G or m22G formation on tRNAs in a substrate-dependent manner. Sci China Life Sci. 2023; 2295-2309.

[124]

WangC, UlryckN, HerzelL, et al. N 2-methylguanosine modifications on human tRNAs and snRNA U6 are important for cell proliferation, protein translation and pre-mRNA splicing. Nucleic Acids Res. 2023; 51(14):7496-7519.

[125]

YangWQ, XiongQP, GeJY, et al. THUMPD3-TRMT112 is a m2G methyltransferase working on a broad range of tRNA substrates. Nucleic Acids Res. 2021; 49(20):11900-11919.

[126]

DaiQ, ZhengG, SchwartzMH, Clark WC, PanT. Selective enzymatic demethylation of N(2), N(2)-dimethylguanosine in rna and its application in high-throughput tRNA sequencing. Angew Chem Int Ed Engl. 2017; 56(18):5017-5020.

[127]

ZhangY, ZhangX, ShiJ, et al. Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs. Nat Cell Biol. 2018; 20(5):535-540.

[128]

DeweJM, FullerBL, LentiniJM, Kellner SM, FuD. TRMT1-catalyzed tRNA modifications are required for redox homeostasis to ensure proper cellular proliferation and oxidative stress survival. Mol Cell Biol. 2017; 37(21):1-21.

[129]

QiTF, MiaoW, WangY. Targeted profiling of Epitranscriptomic reader, writer, and eraser proteins accompanied with Radioresistance in breast cancer cells. Anal Chem. 2022; 94(3):1525-1530.

[130]

ZhangK, Lentini JM, PrevostCT, HashemMO, Alkuraya FS, FuD. An intellectual disability-associated missense variant in TRMT1 impairs tRNA modification and reconstitution of enzymatic activity. Hum Mutat. 2020; 41(3):600-607.

[131]

OlivieraAD, DaiX, MottaghiniaS, et al. Recognition and cleavage of human tRNA methyltransferase TRMT1 by the SARS-CoV-2 main protease. bioRxiv. 2023; 1-27.

[132]

LuJL, ZhouXL. SARS-CoV-2 main protease Nsp5 cleaves and inactivates human tRNA methyltransferase TRMT1. J Mol Cell Biol. 2023; 15(4):1-4.

[133]

HuangY, ChenS, XiaoL, et al. A novel prognostic signature for survival prediction and immune implication based on SARS-CoV-2-related genes in kidney renal clear cell carcinoma. Front Bioeng Biotechnol. 2021; 9:744659.

[134]

Ruiz-ArroyoVM, RajR, BabuK, Onolbaatar O, RobertsPH, NamY. Structures and mechanisms of tRNA methylation by METTL1-WDR4. Nature. 2023; 613(7943):383-390.

[135]

TomikawaC. 7-Methylguanosine modifications in transfer RNA (tRNA). Int J Mol Sci. 2018; 19(12):1-14.

[136]

LinS, LiuQ, LelyveldVS, Choe J, SzostakJW, GregoryRI. Mettl1/Wdr4-mediated m(7)G tRNA methylome is required for Normal mRNA translation and embryonic stem cell self-renewal and differentiation. Mol Cell. 2018; 71(2):244-255.e5.

[137]

OrellanaEA, LiuQ, YankovaE, et al. METTL1-mediated m(7)G modification of Arg-TCT tRNA drives oncogenic transformation. Mol Cell. 2021; 81(16):3323-3338.e14.

[138]

ChenZ, ZhuW, ZhuS, et al. METTL1 promotes hepatocarcinogenesis via m(7) G tRNA modification-dependent translation control. Clin Transl Med. 2021; 11(12):e661.

[139]

HuangM, LongJ, YaoZ, et al. METTL1-mediated m7G tRNA modification promotes Lenvatinib resistance in hepatocellular carcinoma. Cancer Res. 2023; 83(1):89-102.

[140]

LiaoJ, YiY, YueX, et al. Methyltransferase 1 is required for nonhomologous end-joining repair and renders hepatocellular carcinoma resistant to radiotherapy. Hepatology. 2022; 77:1896-1910.

[141]

ZengX, LiaoG, LiS, et al. Eliminating METTL1-mediated accumulation of PMN-MDSCs prevents hepatocellular carcinoma recurrence after radiofrequency ablation. Hepatology. 2022; 77:1122-1138.

[142]

ZhuS, WuY, ZhangX, et al. Targeting N(7)-methylguanosine tRNA modification blocks hepatocellular carcinoma metastasis after insufficient radiofrequency ablation. Mol Ther. 2022; 31:1596-1614.

[143]

LiX, DongH, ChenL, et al. Identification of N7-methylguanosine related subtypes and construction of prognostic model in gastric cancer. Front Immunol. 2022; 13:984149.

[144]

LiXY, WangSL, ChenDH, et al. Construction and validation of a m7G-related gene-based prognostic model for gastric cancer. Front Oncol. 2022; 12:861412.

[145]

HanH, ZhengS, LinS. N(7)-methylguanosine (m(7)G) tRNA modification: a novel autophagy modulator in cancer. Autophagy. 2023; 19(1):360-362.

[146]

HanH, YangC, MaJ, et al. N(7)-methylguanosine tRNA modification promotes esophageal squamous cell carcinoma tumorigenesis via the RPTOR/ULK1/autophagy axis. Nat Commun. 2022; 13(1):1478.

[147]

DaiZ, LiuH, LiaoJ, et al. N(7)-Methylguanosine tRNA modification enhances oncogenic mRNA translation and promotes intrahepatic cholangiocarcinoma progression. Mol Cell. 2021; 81(16):3339-3355.e8.

[148]

García-VílchezR, Añazco-GuenkovaAM, DietmannS, et al. METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer. Mol Cancer. 2023; 22(1):119.

[149]

ChenB, JiangW, HuangY, et al. N(7)-methylguanosine tRNA modification promotes tumorigenesis and chemoresistance through WNT/β-catenin pathway in nasopharyngeal carcinoma. Oncogene. 2022; 41(15):2239-2253.

[150]

MaJ, HanH, HuangY, et al. METTL1/WDR4-mediated m(7)G tRNA modifications and m(7)G codon usage promote mRNA translation and lung cancer progression. Mol Ther. 2021; 29(12):3422-3435.

[151]

ChenJ, LiK, ChenJ, et al. Aberrant translation regulated by METTL1/WDR4-mediated tRNA N7-methylguanosine modification drives head and neck squamous cell carcinoma progression. Cancer Commun (Lond). 2022; 42(3):223-244.

[152]

HuangY, MaJ, YangC, et al. METTL1 promotes neuroblastoma development through m(7)G tRNA modification and selective oncogenic gene translation. Biomark Res. 2022; 10(1):68.

[153]

YingX, LiuB, YuanZ, et al. METTL1-m(7) G-EGFR/EFEMP1 axis promotes the bladder cancer development. Clin Transl Med. 2021; 11(12):e675.

[154]

ChenC, ChaoY, ZhangC, et al. TROP2 translation mediated by dual m6A/m7G RNA modifications promotes bladder cancer development. Cancer Lett. 2023; 566:216246.

[155]

WangZ, YuP, ZouY, et al. METTL1/WDR4-mediated tRNA m7G modification and mRNA translation control promote oncogenesis and doxorubicin resistance. Oncogene. 2023; 42(23):1900-1912.

[156]

DengY, ZhouZ, JiW, LinS, WangM. METTL1-mediated m(7)G methylation maintains pluripotency in human stem cells and limits mesoderm differentiation and vascular development. Stem Cell Res Ther. 2020; 11(1):306.

[157]

ShaheenR, Abdel-Salam GMH, GuyMP, et al. Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism. Genome Biol. 2015; 16:210.

[158]

ChenZ, WangW, HuaY. Expression patterns of eight RNA-modified regulators correlating with immune infiltrates during the progression of osteoarthritis. Front Immunol. 2023; 14:1019445.

[159]

CarterJM, EmmettW, MozosIR, et al. FICC-seq: a method for enzyme-specified profiling of methyl-5-uridine in cellular RNA. Nucleic Acids Res. 2019; 47(19):e113.

[160]

PowellCA, Minczuk M. TRMT2B is responsible for both tRNA and rRNA m(5)U-methylation in human mitochondria. RNA Biol. 2020; 17(4):451-462.

[161]

YamagamiR, Yamashita K, NishimasuH, et al. The tRNA recognition mechanism of folate/FAD-dependent tRNA methyltransferase (TrmFO). J Biol Chem. 2012; 287(51):42480-42494.

[162]

PereiraM, Ribeiro DR, PinheiroMM, FerreiraM, Kellner S, SoaresAR. m(5)U54 tRNA hypomodification by lack of TRMT2A drives the generation of tRNA-derived small RNAs. Int J Mol Sci. 2021; 22(6):1-19.

[163]

JohanssonMJ, Byström AS. Dual function of the tRNA(m(5)U54)methyltransferase in tRNA maturation. RNA. 2002; 8(3):324-335.

[164]

PerssonBC, Gustafsson C, BergDE, BjörkGR. The gene for a tRNA modifying enzyme, m5U54-methyltransferase, is essential for viability in Escherichia coli. Proc Natl Acad Sci U S A. 1992; 89(9):3995-3998.

[165]

RenF, CaoKY, GongRZ, et al. The role of post-transcriptional modification on a new tRNA(Ile(GAU)) identified from Ganoderma lucidum in its fragments’ cytotoxicity on cancer cells. Int J Biol Macromol. 2023; 229:885-895.

[166]

ChangYH, Nishimura S, OishiH, KellyVP, KunoA, TakahashiS. TRMT2A is a novel cell cycle regulator that suppresses cell proliferation. Biochem Biophys Res Commun. 2019; 508(2):410-415.

[167]

LiZ, MaoJ, HuangD, Song B, MengJ. RNADSN: transfer-learning 5-methyluridine (m(5)U) modification on mRNAs from common features of tRNA. Int J Mol Sci. 2022; 23(21):1-10.

[168]

RimbachK, KaiserS, HelmM, Dalpke AH, EigenbrodT. 2’-O-methylation within bacterial RNA acts as suppressor of TLR7/TLR8 activation in human innate immune cells. J Innate Immun. 2015; 7(5):482-493.

[169]

FreundI, BuhlDK, BoutinS, et al. 2’-O-methylation within prokaryotic and eukaryotic tRNA inhibits innate immune activation by endosomal toll-like receptors but does not affect recognition of whole organisms. RNA. 2019; 25(7):869-880.

[170]

KellerP, FreundI, MarchandV, et al. Double methylation of tRNA-U54 to 2’-O-methylthymidine (Tm) synergistically decreases immune response by toll-like receptor 7. Nucleic Acids Res. 2018; 46(18):9764-9775.

[171]

GuyMP, Phizicky EM. Conservation of an intricate circuit for crucial modifications of the tRNAPhe anticodon loop in eukaryotes. RNA. 2015; 21(1):61-74.

[172]

GuyMP, ShawM, WeinerCL, et al. Defects in tRNA anticodon loop 2’-O-methylation are implicated in nonsyndromic X-linked intellectual disability due to mutations in FTSJ1. Hum Mutat. 2015; 36(12):1176-1187.

[173]

LiJ, WangYN, XuBS, et al. Intellectual disability-associated gene ftsj1 is responsible for 2’-O-methylation of specific tRNAs. EMBO Rep. 2020; 21(8):e50095.

[174]

NagayoshiY, ChujoT, HirataS, et al. Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability. Sci Adv. 2021; 7(13):1-15.

[175]

HanL, GuyMP, KonY, Phizicky EM. Lack of 2’-O-methylation in the tRNA anticodon loop of two phylogenetically distant yeast species activates the general amino acid control pathway. PLoS Genet. 2018; 14(3):e1007288.

[176]

DuY, YuanY, XuL, et al. Discovery of METTL3 small molecule inhibitors by virtual screening of natural products. Front Pharmacol. 2022; 13:878135.

[177]

YankovaE, Blackaby W, AlbertellaM, et al. Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature. 2021; 593(7860):597-601.

[178]

Moroz-OmoriEV, HuangD, Kumar BediR, et al. METTL3 inhibitors for Epitranscriptomic modulation of cellular processes. ChemMedChem. 2021; 16(19):3035-3043.

[179]

DolboisA, BediRK, BochenkovaE, et al. 1,4,9-Triazaspiro[5.5]undecan-2-one derivatives as potent and selective METTL3 inhibitors. J Med Chem. 2021; 64(17):12738-12760.

[180]

WangJN, WangF, KeJ, et al. Inhibition of METTL3 attenuates renal injury and inflammation by alleviating TAB3 m6A modifications via IGF2BP2-dependent mechanisms. Sci Transl Med. 2022; 14(640):eabk2709.

[181]

LeeJH, KimS, JinMS, Kim YC. Discovery of substituted indole derivatives as allosteric inhibitors of m(6) A-RNA methyltransferase, METTL3-14 complex. Drug Dev Res. 2022; 83(3):783-799.

[182]

LeeJH, ChoiN, KimS, JinMS, ShenH, Kim YC. Eltrombopag as an allosteric inhibitor of the METTL3-14 complex affecting the m(6)A methylation of RNA in acute myeloid leukemia cells. Pharmaceuticals (Basel). 2022; 15(4):1-18.

[183]

SchaeferM, Hagemann S, HannaK, LykoF. Azacytidine inhibits RNA methylation at DNMT2 target sites in human cancer cell lines. Cancer Res. 2009; 69(20):8127-8132.

[184]

SchwickertM, Fischer TR, ZimmermannRA, et al. Discovery of inhibitors of DNA methyltransferase 2, an Epitranscriptomic modulator and potential target for cancer treatment. J Med Chem. 2022; 65(14):9750-9788.

[185]

ChenB, YeF, YuL, et al. Development of cell-active N6-methyladenosine RNA demethylase FTO inhibitor. J Am Chem Soc. 2012; 134(43):17963-17971.

[186]

LiQ, HuangY, LiuX, GanJ, ChenH, Yang CG. Rhein inhibits AlkB repair enzymes and sensitizes cells to methylated DNA damage. J Biol Chem. 2016; 291(21):11083-11093.

[187]

HuangY, YanJ, LiQ, et al. Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5. Nucleic Acids Res. 2015; 43(1):373-384.

[188]

QiaoY, ZhouB, ZhangM, et al. A novel inhibitor of the obesity-related protein FTO. Biochemistry. 2016; 55(10):1516-1522.

[189]

WangR, HanZ, LiuB, et al. Identification of natural compound radicicol as a potent FTO inhibitor. Mol Pharm. 2018; 15(9):4092-4098.

[190]

HeW, ZhouB, LiuW, et al. Identification of a novel small-molecule binding site of the fat mass and obesity associated protein (FTO). J Med Chem. 2015; 58(18):7341-7348.

[191]

WangY, LiJ, HanX, et al. Identification of Clausine E as an inhibitor of fat mass and obesity-associated protein (FTO) demethylase activity. J Mol Recognit. 2019; 32(10):e2800.

[192]

HanX, WangN, LiJ, WangY, WangR, Chang J. Identification of nafamostat mesilate as an inhibitor of the fat mass and obesity-associated protein (FTO) demethylase activity. Chem Biol Interact. 2019; 297:80-84.

[193]

WangT, HongT, HuangY, et al. Fluorescein derivatives as bifunctional molecules for the simultaneous inhibiting and labeling of FTO protein. J Am Chem Soc. 2015; 137(43):13736-13739.

[194]

PengS, XiaoW, JuD, et al. Identification of entacapone as a chemical inhibitor of FTO mediating metabolic regulation through FOXO1. Sci Transl Med. 2019; 11(488):1-11.

[195]

SelbergS, YuLY, BondarenkoO, et al. Small-molecule inhibitors of the RNA M6A demethylases FTO potently support the survival of dopamine neurons. Int J Mol Sci. 2021; 22(9):1-15.

[196]

HuffS, Kummetha IR, ZhangL, et al. Rational design and optimization of m(6)A-RNA demethylase FTO inhibitors as anticancer agents. J Med Chem. 2022; 65(16):10920-10937.

[197]

SuR, DongL, LiC, et al. R-2HG exhibits anti-tumor activity by targeting FTO/m(6)a/MYC/CEBPA signaling. Cell. 2018; 172(1–2):90-105.e23.

[198]

XieG, WuXN, LingY, et al. A novel inhibitor of N (6)-methyladenosine demethylase FTO induces mRNA methylation and shows anti-cancer activities. Acta Pharm Sin B. 2022; 12(2):853-866.

[199]

SunK, duY, HouY, et al. Saikosaponin D exhibits anti-leukemic activity by targeting FTO/m(6)A signaling. Theranostics. 2021; 11(12):5831-5846.

[200]

HuangY, SuR, ShengY, et al. Small-molecule targeting of oncogenic FTO demethylase in acute myeloid leukemia. Cancer Cell. 2019; 35(4):677-691.e10.

[201]

SuR, DongL, LiY, et al. Targeting FTO suppresses cancer stem cell maintenance and immune evasion. Cancer Cell. 2020; 38(1):79-96.e11.

[202]

LiuY, LiangG, XuH, et al. Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance. Cell Metab. 2021; 33(6):1221-1233.e11.

[203]

FangZ, MuB, LiuY, et al. Discovery of a potent, selective and cell active inhibitor of m(6)A demethylase ALKBH5. Eur J Med Chem. 2022; 238:114446.

[204]

SelbergS, SeliN, KankuriE, Karelson M. Rational Design of Novel Anticancer Small-Molecule RNA m6A demethylase ALKBH5 inhibitors. ACS Omega. 2021; 6(20):13310-13320.

[205]

MalacridaA, RivaraM, di DomizioA, et al. 3D proteome-wide scale screening and activity evaluation of a new ALKBH5 inhibitor in U87 glioblastoma cell line. Bioorg Med Chem. 2020; 28(4):115300.

[206]

MalacridaA, di Domizio A, BentivegnaA, et al. MV1035 overcomes temozolomide resistance in patient-derived glioblastoma stem cell lines. Biology (Basel). 2022; 11(1):1-12.

[207]

LiN, KangY, WangL, et al. ALKBH5 regulates anti-PD-1 therapy response by modulating lactate and suppressive immune cell accumulation in tumor microenvironment. Proc Natl Acad Sci U S A. 2020; 117(33):20159-20170.

[208]

ChenJ, XuC, YangK, et al. Inhibition of ALKBH5 attenuates I/R-induced renal injury in male mice by promoting Ccl28 m6A modification and increasing Treg recruitment. Nat Commun. 2023; 14(1):1161.

[209]

NigamR, BabuKR, GhoshT, et al. Indenone derivatives as inhibitor of human DNA dealkylation repair enzyme AlkBH3. Bioorg Med Chem. 2018; 26(14):4100-4112.

[210]

NakaoS, Mabuchi M, ShimizuT, et al. Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs. Bioorg Med Chem Lett. 2014; 24(4):1071-1074.

[211]

UedaM, Shimizu T, MabuchiM, et al. Novel metabolically stable PCA-1/ALKBH3 inhibitor has potent antiproliferative effects on DU145 cells in vivo. Anticancer Res. 2018; 38(1):211-218.

[212]

ChuaGNL, Wassarman KL, SunH, et al. Cytosine-based TET enzyme inhibitors. ACS Med Chem Lett. 2019; 10(2):180-185.

[213]

WeirathNA, HurbenAK, ChaoC, et al. Small molecule inhibitors of TET dioxygenases: Bobcat339 activity is mediated by contaminating copper(II). ACS Med Chem Lett. 2022; 13(5):792-798.

[214]

CaoK, duY, BaoX, et al. Glutathione-bioimprinted nanoparticles targeting of N6-methyladenosine FTO demethylase as a strategy against leukemic stem cells. Small. 2022; 18(13):e2106558.

[215]

ChengP, HanH, ChenF, et al. Amelioration of acute myocardial infarction injury through targeted ferritin nanocages loaded with an ALKBH5 inhibitor. Acta Biomater. 2022; 140:481-491.

[216]

SinghA, SinghV, WallisN, et al. Development of a novel IGF2BP1 inhibitor as metastasis-specific therapeutic agent. Eur J Cancer. 2022; 174: S104-S105.

[217]

MahapatraL, Andruska N, MaoC, leJ, Shapiro DJ. A novel IMP1 inhibitor, BTYNB, targets c-Myc and inhibits melanoma and ovarian cancer cell proliferation. Transl Oncol. 2017; 10(5):818-827.

[218]

MüllerS, BleyN, BuschB, et al. The oncofetal RNA-binding protein IGF2BP1 is a druggable, post-transcriptional super-enhancer of E2F-driven gene expression in cancer. Nucleic Acids Res. 2020; 48(15):8576-8590.

[219]

LiuY, GuoQ, YangH, et al. Allosteric regulation of IGF2BP1 as a novel strategy for the activation of tumor immune microenvironment. ACS Cent Sci. 2022; 8(8):1102-1115.

[220]

SelbergS, Blokhina D, AatonenM, et al. Discovery of small molecules that activate RNA methylation through cooperative binding to the METTL3-14-WTAP complex active site. Cell Rep. 2019; 26(13):3762-3771.e5.

[221]

Abbasi-MohebL, MertelS, GonsiorM, et al. Mutations in NSUN2 cause autosomal-recessive intellectual disability. Am J Hum Genet. 2012; 90(5):847-855.

[222]

KhanMA, RafiqMA, NoorA, et al. Mutation in NSUN2, which encodes an RNA methyltransferase, causes autosomal-recessive intellectual disability. Am J Hum Genet. 2012; 90(5):856-863.

[223]

HuffS, TiwariSK, GonzalezGM, Wang Y, RanaTM. M(6)A-RNA demethylase FTO inhibitors impair self-renewal in glioblastoma stem cells. ACS Chem Biol. 2021; 16(2):324-333.

[224]

LiF, Kennedy S, HajianT, et al. A radioactivity-based assay for screening human m6A-RNA methyltransferase, METTL3-METTL14 complex, and demethylase ALKBH5. J Biomol Screen. 2016; 21(3):290-297.

RIGHTS & PERMISSIONS

2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.

AI Summary AI Mindmap
PDF

193

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/