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Description

N6-adenosine-methyltransferase catalytic subunit (UniProt: Q86U44, also known as EC:2.1.1.348, Methyltransferase-like protein 3, hMETTL3, N6-adenosine-methyltransferase 70 kDa subunit, MT-A70) is encoded by the METTL3 (also known as MTA70) gene (Gene ID: 56339) in human. METTL3 heterodimerizes with METTL14 to form an antiparallel heterodimer, which constitutes an active methyltransferase that methylates adenosine residues at the N6 position of some RNAs and regulates various cellular processes, including differentiation of embryonic and hematopoietic stem cells, cortical neurogenesis, differentiation of T-cells, and primary miRNA processing. In response to UV caused DNA damage, METTL3 rapidly catalyzes the formation of m6A on poly(A) transcripts at DNA damage sites that leads to the recruitment of POLK to these sites. It is localized both in the cytoplasm and in the nucleus. It colocalizes with speckles in interphase nuclei. In response to UV irradiation, it is shown to colocalize to DNA damage sites. Its methyltransferase activity is inhibited by sumoylation. However, sumoylation does not affect its subcellular location or interaction with METTL14. Overexpression of METTL3 is reported in several human cancers and its knockdown is known to promote apoptosis. METTL3 is reported to be strongly and directly phosphorylated by ERK2 at serine 43, 50, and 525 and to a lesser extent by p38 and JNK. METTL3 phosphorylation increases its USP5-mediated deubiquitination that leads to its stabilization. Phosphorylation of METTL3 is reported to promote murine embryonic stem cell differentiation. This polyclonal antibody specifically recognizes METTL3 phosphorylated at serine 43 and does not detect mutant forms where serine is replaced by alanine residues. (Ref.: Sun, H-L., et al. (2020). Mol. Cell. 80(4), 633-647, Wang, P., et al. (2016). Mol. Cell. 63(2), 306-317, Lin, S., et al. (2016). Mol. Cell. 62(3), 335-345, Wang, X. et al. (2014). Nature. 505(7481), 117-120).