Anti-METTL3 Antibody Picoband® Fluoro488 Conjugated

N6-adenosine-methyltransferase 70 kDa subunit (METTL3) is an enzyme that in humans is encoded by the METTL3 gene. It is mapped to 14q11.2. This gene encodes the 70 kDa subunit of MT-A which is part of N6-adenosine-methyltransferase. This enzyme is involved in the posttranscriptional methylation of internal adenosine residues in eukaryotic mRNAs, forming N6-methyladenosine.

A synthetic peptide corresponding to a sequence at the C-terminus of human METTL3, which shares 100% and 95.3% amino acid (aa) sequence identity with mouse and rat METTL3, respectively.

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 haematopoietic 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:27627798, PubMed:27373337, PubMed:27281194, PubMed:28297716, PubMed:9409616) . In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core (PubMed:27627798, PubMed:27373337, PubMed:27281194) . 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 regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (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) . M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs) (PubMed:25799998) . 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 to cancer cell proliferation by promoting mRNA translation (PubMed:27117702) .

1. Alarcon, C. R., Lee, H., Goodarzi, H., Halberg, N., Tavazoie, S. F. N (6) -methyladenosine marks primary microRNAs for processing. Nature 519: 482-485, 2015. 2. Barbieri, I., Tzelepis, K., Pandolfini, L., Shi, J., Millan-Zambrano, G., Robson, S. C., Aspris, D., Migliori, V., Bannister, A. J., Han, N., De Braekeleer, E., Ponstingl, H., Hendrick, A., Vakoc, C. R., Vassiliou, G. S., Kouzarides, T.Promoter-bound METTL3 maintains myeloid leukaemia by m (6) A-dependent translation control. Nature 552: 126-131, 2017. 3. Bujnicki, J. M., Feder, M., Radlinska, M., Blumenthal, R. M. Structure prediction and phylogenetic analysis of a functionally diverse family of proteins homologous to the MT-A70 subunit of the human mRNA:m6A methyltransferase. J. Molec. Evol. 55: 431-444, 2002.