METTL3
GeneName
METTL3
Summary
METTL3, also known as methyltransferase like 3, Ime4, or methyltransferase like protein 3, is a 64 kDa RNA N6-methyladenosine methyltransferase that plays a crucial role in the regulation of mRNA metabolism. It is predominantly localised in the nucleus, particularly within nuclear bodies and speckles, but is also found in the cytosol and Golgi apparatus. METTL3 is involved in various processes such as mRNA modification, processing, and splicing, and is essential for the methylation of adenosine residues in mRNA, which influences mRNA stability and translation efficiency. Additionally, it has roles in cellular responses to UV damage, circadian rhythms, and the differentiation of various cell types, including hematopoietic stem cells and forebrain radial glial cells.
Importance
METTL3 is relevant to: - The regulation of gene expression through mRNA methylation, impacting translation and stability of mRNA - Developmental processes such as gliogenesis and spermatogenesis, where precise control of gene expression is vital - Immune responses, particularly in the context of innate immunity and T cell differentiation - Cancer research, as alterations in mRNA methylation patterns can influence oncogenic processes and tumour progression - Understanding circadian rhythms and their impact on cellular function and health
Top Products
For researchers investigating METTL3, we highly recommend the top-selling recombinant antibody, Anti-METTL3 antibody [EPR18810] (ab195352). This antibody has been validated in knockout models, ensuring reliable performance in various applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), immunoprecipitation (IP), and flow cytometry (FC). With 435 citations, it is well-regarded in the research community, making it an excellent choice for those seeking dependable METTL3 detection. The Recombinant Human METTL3 protein ELISA Kit (ab163377), supported by 1 citation, offers a reliable option for researchers looking to measure METTL3 levels in their experiments.
Abcam Product Citation Summary
The data indicates that METTL3 is a significant target in various studies related to cancer, particularly in human hepatocellular carcinoma (HCC) and bladder cancer. Additionally, research involving mouse models highlights its role in Alzheimer's disease, innate immunity, and infertility. The use of multiple applications, including Western blotting and immunohistochemistry, suggests a comprehensive approach to understanding METTL3's functions and interactions in different biological contexts.
Abcam Product Citation Table
Domain
Gate loop 1 and gate loop 2 regions are adjacent to the S-adenosyl-L-homocysteine-binding site and display large conformational changes upon ligand-binding. They may play an important role in adenosine recognition. The interface loop contributes to the heterodimer interaction.
Function
The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, differentiation of embryonic and hematopoietic stem cells, cortical neurogenesis, response to DNA damage, differentiation of T-cells and primary miRNA processing (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:27281194, PubMed:27373337, PubMed:27627798, PubMed:28297716, PubMed:29348140, PubMed:29506078, PubMed:30428350, PubMed:9409616). In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core (PubMed:27281194, PubMed:27373337, PubMed:27627798). N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability, processing, translation efficiency and editing (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:28297716, PubMed:9409616). M6A acts as a key regulator of mRNA stability: methylation is completed upon the release of mRNA into the nucleoplasm and promotes mRNA destabilization and degradation (PubMed:28637692). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization, promoting differentiation of ESCs (By similarity). M6A regulates the length of the circadian clock: acts as an early pace-setter in the circadian loop by putting mRNA production on a fast-track for facilitating nuclear processing, thereby providing an early point of control in setting the dynamics of the feedback loop (By similarity). M6A also regulates circadian regulation of hepatic lipid metabolism (PubMed:30428350). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (By similarity). Also required for oogenesis (By similarity). Involved in the response to DNA damage: in response to ultraviolet irradiation, METTL3 rapidly catalyzes the formation of m6A on poly(A) transcripts at DNA damage sites, leading to the recruitment of POLK to DNA damage sites (PubMed:28297716). M6A is also required for T-cell homeostasis and differentiation: m6A methylation of transcripts of SOCS family members (SOCS1, SOCS3 and CISH) in naive T-cells promotes mRNA destabilization and degradation, promoting T-cell differentiation (By similarity). Inhibits the type I interferon response by mediating m6A methylation of IFNB (PubMed:30559377). M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs) (PubMed:25799998). Mediates m6A methylation of Xist RNA, thereby participating in random X inactivation: m6A methylation of Xist leads to target YTHDC1 reader on Xist and promote transcription repression activity of Xist (PubMed:27602518). M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells (By similarity). METTL3 mediates methylation of pri-miRNAs, marking them for recognition and processing by DGCR8 (PubMed:25799998). Acts as a positive regulator of mRNA translation independently of the methyltransferase activity: promotes translation by interacting with the translation initiation machinery in the cytoplasm (PubMed:27117702). Its overexpression in a number of cancer cells suggests that it may participate in cancer cell proliferation by promoting mRNA translation (PubMed:27117702). During human coronavirus SARS-CoV-2 infection, adds m6A modifications in SARS-CoV-2 RNA leading to decreased RIGI binding and subsequently dampening the sensing and activation of innate immune responses (PubMed:33961823).
Post-translational modifications
Sumoylation inhibits the N6-adenosine-methyltransferase activity. Sumoylation does not affect subcellular location or interaction with METTL14. Desumoylated by SENP1.
Sequence Similarities
Belongs to the MT-A70-like family.
Tissue Specificity
Widely expressed at low level. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes.
Cellular localization
- Nucleus
- Nucleus speckle
- Cytoplasm
- Colocalizes with speckles in interphase nuclei, suggesting that it may be associated with nuclear pre-mRNA splicing components (PubMed:9409616). In response to ultraviolet irradiation, colocalizes to DNA damage sites however, it probably does not bind DNA but localizes in the vicinity of DNA damage sites (PubMed:28297716).
Alternative names
MTA70, METTL3, N(6)-adenosine-methyltransferase catalytic subunit METTL3, Methyltransferase-like protein 3, N(6)-adenosine-methyltransferase 70 kDa subunit, hMETTL3, MT-A70