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Molecular and cellular biochemistry
Jan 24, 2025;

METTL3: a multifunctional regulator in diseases.

Na Li, Xiang Wei, Jian Dai, Jinfeng Yang, Sizheng Xiong
Author Information
  1. Na Li: Division of Cardiothoracic and Vascular Surgery, Sino-Swiss Heart-Lung Transplantation Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  2. Xiang Wei: Division of Cardiothoracic and Vascular Surgery, Sino-Swiss Heart-Lung Transplantation Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  3. Jian Dai: Department of Critical Care Medicine, Wuhan Wuchang Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, China.
  4. Jinfeng Yang: Department of Medical Affairs, Wuhan Wuchang Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, China. 742585313@qq.com.
  5. Sizheng Xiong: Department of Vascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. Rmxiongsz@outlook.com.
PMID: 39853661 DOI: 10.1007/s11010-025-05208-z

Abstract

N6-methyladenosine (mA) methylation is the most prevalent and abundant internal modification of mRNAs and is catalyzed by the methyltransferase complex. Methyltransferase-like 3 (METTL3), the best-known mA methyltransferase, has been confirmed to function as a multifunctional regulator in the reversible epitranscriptome modulation of mA modification according to follow-up studies. Accumulating evidence in recent years has shown that METTL3 can regulate a variety of functional genes, that aberrant expression of METTL3 is usually associated with many pathological conditions, and that its expression regulatory mechanism is related mainly to its methyltransferase activity or mRNA posttranslational modification. In this review, we discuss the regulatory functions of METTL3 in various diseases, including metabolic diseases, cardiovascular diseases, and cancer. We focus mainly on recent progress in identifying the downstream target genes of METTL3 and its underlying molecular mechanisms and regulators in the above systems. Studies have revealed that the use of METTL3 as a therapeutic target and a new diagnostic biomarker has broad prospects. We hope that this review can serve as a reference for further studies.

Keywords

Cancer Cardiovascular diseases Drug therapy METTL3 Metabolic diseases m6A

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Created with Highcharts 10.0.0METTL3diseasesmAmodificationmethyltransferasemultifunctionalregulatorstudiesrecentcangenesexpressionregulatorymainlyreviewtargetN6-methyladenosinemethylationprevalentabundantinternalmRNAscatalyzedcomplexMethyltransferase-like3best-knownconfirmedfunctionreversibleepitranscriptomemodulationaccordingfollow-upAccumulatingevidenceyearsshownregulatevarietyfunctionalaberrantusuallyassociatedmanypathologicalconditionsmechanismrelatedactivitymRNAposttranslationaldiscussfunctionsvariousincludingmetaboliccardiovascularcancerfocusprogressidentifyingdownstreamunderlyingmolecularmechanismsregulatorssystemsStudiesrevealedusetherapeuticnewdiagnosticbiomarkerbroadprospectshopeservereferenceMETTL3:CancerCardiovascularDrugtherapyMetabolicm6A

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