METTL3 from Target Validation to the First Small-Molecule Inhibitors: A Medicinal Chemistry Journey

Discovery of substituted indole derivatives as allosteric inhibitors of m 6 A‐RNA methyltransferase, METTL3 ‐14 complex

(2022) Je‐Heon Lee et al.   DRUG DEVELOPMENT RESEARCH

Anti-HIV drug elvitegravir suppresses cancer metastasis via increased proteasomal degradation of m6A methyltransferase METTL3

(2022) Long Liao et al.   CANCER RESEARCH

JNK Signaling Promotes Bladder Cancer Immune Escape by Regulating METTL3-Mediated m6A Modification of PD-L1 mRNA

(2022) Zegui Ni et al.   CANCER RESEARCH

The Mettl3 epitranscriptomic writer amplifies p53 stress responses

(2022) Nitin Raj et al.   MOLECULAR CELL

Discovery of METTL3 Small Molecule Inhibitors by Virtual Screening of Natural Products

(2022) Yue Du et al.   Frontiers in Pharmacology

Eltrombopag as an Allosteric Inhibitor of the METTL3-14 Complex Affecting the m6A Methylation of RNA in Acute Myeloid Leukemia Cells

(2022) Je-Heon Lee et al.   Pharmaceuticals

METTL3 promotes the growth and metastasis of pancreatic cancer by regulating the m6A modification and stability of E2F5

(2022) Yan Tang et al.   CELLULAR SIGNALLING

Alternative splicing of METTL3 explains apparently METTL3-independent m6A modifications in mRNA

(2022) Hui Xian Poh et al.   PLOS BIOLOGY

m6A Methylation in Cardiovascular Diseases: From Mechanisms to Therapeutic Potential

(2022) Longbo Li et al.   Frontiers in Genetics

METTL3 promotes non-small cell lung cancer (NSCLC) cell proliferation and colony formation in a m6A-YTHDF1 dependent way

(2022) Xuejun Dou et al.   BMC Pulmonary Medicine

Ythdf is a N6‐methyladenosine reader that modulates Fmr1 target mRNA selection and restricts axonal growth in Drosophila

(2021) Lina Worpenberg et al.   EMBO JOURNAL

Metformin exhibits antiproliferation activity in breast cancer via miR-483-3p/METTL3/m6A/p21 pathway

(2021) Lin Cheng et al.   Oncogenesis

SEDT2/METTL14-mediated m6A methylation awakening contributes to hypoxia-induced pulmonary arterial hypertension in mice

(2021) Xue-Liang Zhou et al.   Aging-US

Eltrombopag for the treatment of refractory thrombocytopenia associated with connective tissue disease

(2021) Juan Wang et al.   Scientific Reports

Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia

(2021) Eliza Yankova et al.   NATURE

METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection

(2021) Na Li et al.   Cell Reports

Deciphering Epitranscriptome: Modification of mRNA Bases Provides a New Perspective for Post-transcriptional Regulation of Gene Expression

(2021) Suresh Kumar et al.   Frontiers in Cell and Developmental Biology

Rational Design of Novel Anticancer Small-Molecule RNA m6A Demethylase ALKBH5 Inhibitors

(2021) Simona Selberg et al.   ACS Omega

METTL3 Inhibitors for Epitranscriptomic Modulation of Cellular Processes

(2021) Elena V. Moroz‐Omori et al.   ChemMedChem

m6A RNA methylation and beyond – The epigenetic machinery and potential treatment options

(2021) Sabrina Garbo et al.   DRUG DISCOVERY TODAY

Targeting the m6A RNA modification pathway blocks SARS-CoV-2 and HCoV-OC43 replication

(2021) Hannah M. Burgess et al.   GENES & DEVELOPMENT

Emerging Therapeutic Potential of SIRT6 Modulators

(2021) Francesco Fiorentino et al.   JOURNAL OF MEDICINAL CHEMISTRY

1,4,9-Triazaspiro[5.5]undecan-2-one Derivatives as Potent and Selective METTL3 Inhibitors

(2021) Aymeric Dolbois et al.   JOURNAL OF MEDICINAL CHEMISTRY

New insight into the catalytic -dependent and -independent roles of METTL3 in sustaining aberrant translation in chronic myeloid leukemia

(2021) Zaira Ianniello et al.   Cell Death & Disease

The Epigenetic Landscape of Vascular Calcification: An Integrative Perspective

(2020) Yi-Chou Hou et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

N6-methyladenosine modification enables viral RNA to escape recognition by RNA sensor RIG-I

(2020) Mijia Lu et al.   Nature Microbiology

Small‐Molecule Inhibitors of METTL3, the Major Human Epitranscriptomic Writer

(2020) Rajiv K. Bedi et al.   ChemMedChem

The potential role of RNA N6-methyladenosine in Cancer progression

(2020) Tianyi Wang et al.   Molecular Cancer

Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion

(2020) Rui Su et al.   CANCER CELL

A Unified Model for the Function of YTHDF Proteins in Regulating m6A-Modified mRNA

(2020) Sara Zaccara et al.   CELL

A birds'‐eye view of the activity and specificity of the mRNA m 6 A methyltransferase complex

(2020) David Garcias Morales et al.   Wiley Interdisciplinary Reviews-RNA

Reduced Expression of METTL3 Promotes Metastasis of Triple-Negative Breast Cancer by m6A Methylation-Mediated COL3A1 Up-Regulation

(2020) Yu Shi et al.   Frontiers in Oncology

m 6 A RNA methyltransferases METTL3/14 regulate immune responses to anti‐PD‐1 therapy

(2020) Lingling Wang et al.   EMBO JOURNAL

m 6 A transferase METTL3‐induced lncRNA ABHD11‐AS1 promotes the Warburg effect of non‐small‐cell lung cancer

(2020) Lei Xue et al.   JOURNAL OF CELLULAR PHYSIOLOGY

The piRNA CHAPIR regulates cardiac hypertrophy by controlling METTL3-dependent N6-methyladenosine methylation of Parp10 mRNA

(2020) Xiang-Qian Gao et al.   NATURE CELL BIOLOGY

Recent advances in epigenetic proteolysis targeting chimeras (Epi-PROTACs)

(2020) Daniela Tomaselli et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

RNA N6-Methyladenosine Methyltransferase METTL3 Facilitates Colorectal Cancer by Activating the m6A-GLUT1-mTORC1 Axis and Is a Therapeutic Target

(2020) Huarong Chen et al.   GASTROENTEROLOGY

The N 6 -Methyladenosine mRNA Methylase METTL3 Controls Cardiac Homeostasis and Hypertrophy

(2019) Lisa E. Dorn et al.   CIRCULATION

The m6A methyltransferase METTL3 promotes bladder cancer progression via AFF4/NF-κB/MYC signaling network

(2019) Maosheng Cheng et al.   ONCOGENE

METTL3 promotes the proliferation and mobility of gastric cancer cells

(2019) Sen Lin et al.   Open Medicine

Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally

(2019) Huilin Huang et al.   NATURE

Mettl3 Regulates Osteogenic Differentiation and Alternative Splicing of Vegfa in Bone Marrow Mesenchymal Stem Cells

(2019) Cheng Tian et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

The Critical Role of RNA m6A Methylation in Cancer

(2019) Qing Lan et al.   CANCER RESEARCH

METTL3 and ALKBH5 oppositely regulate m6A modification of TFEB mRNA, which dictates the fate of hypoxia/reoxygenation-treated cardiomyocytes

(2019) Huiwen Song et al.   Autophagy

A Reader-Based Assay for m6A Writers and Erasers

(2019) Lars Wiedmer et al.   ANALYTICAL CHEMISTRY

Small-Molecule Targeting of Oncogenic FTO Demethylase in Acute Myeloid Leukemia

(2019) Yue Huang et al.   CANCER CELL

METTL3 promote tumor proliferation of bladder cancer by accelerating pri-miR221/222 maturation in m6A-dependent manner

(2019) Jie Han et al.   Molecular Cancer

METTL3 facilitates tumor progression via an m6A-IGF2BP2-dependent mechanism in colorectal carcinoma

(2019) Ting Li et al.   Molecular Cancer

The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112

(2019) Nhan van Tran et al.   NUCLEIC ACIDS RESEARCH

m6A methyltransferase METTL3 suppresses colorectal cancer proliferation and migration through p38/ERK pathways

(2019) Ru Deng et al.   OncoTargets and Therapy

RNA m6A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail

(2019) Xinyao Lin et al.   Nature Communications

FMRP Modulates Neural Differentiation through m6A-Dependent mRNA Nuclear Export

(2019) Brittany M. Edens et al.   Cell Reports

Regulation of Viral Infection by the RNA Modification N6-methyladenosine

(2019) Graham D. Williams et al.   Annual Review of Virology

The m6A methyltransferase METTL3 promotes osteosarcoma progression by regulating the m6A level of LEF1

(2019) Wujun Miao et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

N6-methyladenosine METTL3 promotes the breast cancer progression via targeting Bcl-2

(2019) Hong Wang et al.   GENE

Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway

(2019) Wen Peng et al.   JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

Site-specific m6A editing

(2019) Jiangbo Wei et al.   Nature Chemical Biology

Reading, writing and erasing mRNA methylation

(2019) Sara Zaccara et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

The RNA m6A methyltransferase METTL3 promotes pancreatic cancer cell proliferation and invasion

(2019) Tianfang Xia et al.   PATHOLOGY RESEARCH AND PRACTICE

The RNA-binding protein FMRP facilitates the nuclear export of N6-methyladenosine–containing mRNAs

(2019) Phillip J. Hsu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

RNA m6A Methyltransferase METTL3 Promotes The Growth Of Prostate Cancer By Regulating Hedgehog Pathway

(2019) Jiarong Cai et al.   OncoTargets and Therapy

Changes in m6A RNA methylation contribute to heart failure progression by modulating translation

(2019) Tea Berulava et al.   EUROPEAN JOURNAL OF HEART FAILURE

METTL14-dependent m6A regulates vascular calcification induced by indoxyl sulfate

(2019) Jing Chen et al.   LIFE SCIENCES

HBXIP-elevated methyltransferase METTL3 promotes the progression of breast cancer via inhibiting tumor suppressor let-7g

(2018) Xiaoli Cai et al.   CANCER LETTERS

METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA m 6 A Modification

(2018) Hengyou Weng et al.   Cell Stem Cell

ALKBH5 Inhibits Pancreatic Cancer Motility by Decreasing Long Non-Coding RNA KCNK15-AS1 Methylation

(2018) Yuan He et al.   CELLULAR PHYSIOLOGY AND BIOCHEMISTRY

Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d

(2018) Philip Knuckles et al.   GENES & DEVELOPMENT

Epigenetics and epitranscriptomics in temporal patterning of cortical neural progenitor competence

(2018) Ki-Jun Yoon et al.   JOURNAL OF CELL BIOLOGY

The RNA Methyltransferase Complex of WTAP, METTL3, and METTL14 Regulates Mitotic Clonal Expansion in Adipogenesis

(2018) Masatoshi Kobayashi et al.   MOLECULAR AND CELLULAR BIOLOGY

Interactions, localization, and phosphorylation of the m 6 A generating METTL3–METTL14–WTAP complex

(2018) Eva Schöller et al.   RNA

Transient N-6-Methyladenosine Transcriptome Sequencing Reveals a Regulatory Role of m6A in Splicing Efficiency

(2018) Annita Louloupi et al.   Cell Reports

METTL3 promotes ovarian carcinoma growth and invasion through the regulation of AXL translation and epithelial to mesenchymal transition

(2018) Wenfeng Hua et al.   GYNECOLOGIC ONCOLOGY

Protein synthesis levels are increased in a subset of individuals with fragile X syndrome

(2018) Sébastien Jacquemont et al.   HUMAN MOLECULAR GENETICS

Fragile X mental retardation protein modulates the stability of its m6A-marked messenger RNA targets

(2018) Feiran Zhang et al.   HUMAN MOLECULAR GENETICS

Structural Basis for Regulation of METTL16, an S-Adenosylmethionine Homeostasis Factor

(2018) Katelyn A. Doxtader et al.   MOLECULAR CELL

mRNA circularization by METTL3–eIF3h enhances translation and promotes oncogenesis

(2018) Junho Choe et al.   NATURE

METTL3 regulates WTAP protein homeostasis

(2018) Melissa Sorci et al.   Cell Death & Disease

The m6A Writer: Rise of a Machine for Growing Tasks

(2018) Dario L. Balacco et al.   BIOCHEMISTRY

N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation

(2018) Honghui Ma et al.   Nature Chemical Biology

Mettl3-mediated m6A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis

(2018) Yunshu Wu et al.   Nature Communications

Fat mass and obesity-associated (FTO) protein regulates adult neurogenesis

(2017) Liping Li et al.   HUMAN MOLECULAR GENETICS

The epitranscriptome m6A writer METTL3 promotes chemo- and radioresistance in pancreatic cancer cells

(2017) Kosuke Taketo et al.   INTERNATIONAL JOURNAL OF ONCOLOGY

RNA Chemical Proteomics Reveals the N6-Methyladenosine (m6A)-Regulated Protein–RNA Interactome

(2017) A. Emilia Arguello et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control

(2017) Isaia Barbieri et al.   NATURE

The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells

(2017) Ly P Vu et al.   NATURE MEDICINE

N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis

(2017) Raghu R Edupuganti et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia

(2017) Danielle M. Townsley et al.   NEW ENGLAND JOURNAL OF MEDICINE

Essential role of METTL3-mediated m6A modification in glioma stem-like cells maintenance and radioresistance

(2017) A Visvanathan et al.   ONCOGENE

ALKBH5-dependent m6A demethylation controls splicing and stability of long 3′-UTR mRNAs in male germ cells

(2017) Chong Tang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis

(2017) Raghu R Edupuganti et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

m 6 A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells

(2017) Qi Cui et al.   Cell Reports

Region-specific RNA m 6 A methylation represents a new layer of control in the gene regulatory network in the mouse brain

(2017) Mengqi Chang et al.   Open Biology

N6 -Methyladenosine in Flaviviridae Viral RNA Genomes Regulates Infection

(2016) Nandan S. Gokhale et al.   Cell Host & Microbe

METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulatingN6-methyladenosine-dependent primary MicroRNA processing

(2016) Jin-zhao Ma et al.   HEPATOLOGY

Feeling Nature’s PAINS: Natural Products, Natural Product Drugs, and Pan Assay Interference Compounds (PAINS)

(2016) Jonathan B. Baell   JOURNAL OF NATURAL PRODUCTS

Nuclear m 6 A Reader YTHDC1 Regulates mRNA Splicing

(2016) Wen Xiao et al.   MOLECULAR CELL

Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases

(2016) Ping Wang et al.   MOLECULAR CELL

The m 6 A Methyltransferase METTL3 Promotes Translation in Human Cancer Cells

(2016) Shuibin Lin et al.   MOLECULAR CELL

Structural basis of N6-adenosine methylation by the METTL3–METTL14 complex

(2016) Xiang Wang et al.   NATURE

The suppressor of cytokine signaling 2 (SOCS2) inhibits tumor metastasis in hepatocellular carcinoma

(2016) Meiling Cui et al.   TUMOR BIOLOGY

Structural insights into the molecular mechanism of the m6A writer complex

(2016) Paweł Śledź et al.   eLife

Structural Basis for the Discriminative Recognition ofN6-Methyladenosine RNA by the Human YT521-B Homology Domain Family of Proteins

(2015) Chao Xu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Structure and Thermodynamics of N6-Methyladenosine in RNA: A Spring-Loaded Base Modification

(2015) Caroline Roost et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

N6-methyladenosine marks primary microRNAs for processing

(2015) Claudio R. Alarcón et al.   NATURE

Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome

(2015) Bastian Linder et al.   NATURE METHODS

Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase

(2014) Xiao-Li Ping et al.   CELL RESEARCH

m6A RNA Modification Controls Cell Fate Transition in Mammalian Embryonic Stem Cells

(2014) Pedro J. Batista et al.   Cell Stem Cell

Methylation by NSun2 Represses the Levels and Function of MicroRNA 125b

(2014) S. Yuan et al.   MOLECULAR AND CELLULAR BIOLOGY

The dynamic epitranscriptome: N6-methyladenosine and gene expression control

(2014) Kate D. Meyer et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Transcriptome-wide N6-methyladenosine profiling of rice callus and leaf reveals the presence of tissue-specific competitors involved in selective mRNA modification

(2014) Yuli Li et al.   RNA Biology

Perturbation of m6A Writers Reveals Two Distinct Classes of mRNA Methylation at Internal and 5′ Sites

(2014) Schraga Schwartz et al.   Cell Reports

m6A mRNA Methylation: A New Circadian Pacesetter

(2013) Michael H. Hastings   CELL

N6-methyladenosine-dependent regulation of messenger RNA stability

(2013) Xiao Wang et al.   NATURE

A METTL3–METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation

(2013) Jianzhao Liu et al.   Nature Chemical Biology

FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA

(2013) Ye Fu et al.   Nature Communications

Eltrombopag inhibits the proliferation of leukemia cells via reduction of intracellular iron and induction of differentiation

(2012) M. Roth et al.   BLOOD

Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons

(2012) Kate D. Meyer et al.   CELL

ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility

(2012) Guanqun Zheng et al.   MOLECULAR CELL

The birth of the Epitranscriptome: deciphering the function of RNA modifications

(2012) Yogesh Saletore et al.   GENOME BIOLOGY

FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism

(2011) Jennifer C. Darnell et al.   CELL

The YTH Domain Is a Novel RNA Binding Domain

(2010) Zhaiyi Zhang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Yeast targets for mRNA methylation

(2010) Zsuzsanna Bodi et al.   NUCLEIC ACIDS RESEARCH

Nuclear Degradation of Wilms Tumor 1-associating Protein and Survivin Splice Variant Switching Underlie IGF-1-mediated Survival

(2009) Theodore W. Small et al.   JOURNAL OF BIOLOGICAL CHEMISTRY