METTL3 Protein, Human (sf9, FLAG)

The METTL3-METTL14 heterodimer functions as an N6-methyltransferase complex that catalyzes adenosine methylation (m6A) at the N(6) position of RNAs, regulating processes including circadian rhythm, stem cell differentiation, DNA damage response, T-cell differentiation, and primary miRNA processing. METTL3 serves as the catalytic core, mediating m6A modifications at 5'-[AG]GAC-3' consensus sites of mRNAs to influence stability, processing, translation efficiency, and editing. m6A destabilizes pluripotency transcripts to promote embryonic stem cell differentiation (by similar), accelerates nuclear mRNA processing as an early circadian pace-setter (by similar), and modulates hepatic lipid metabolism (PubMed:30428350), spermatogenesis (by similar), and oogenesis (by similar). During DNA damage response, METTL3 rapidly generates m6A on poly(A) transcripts to recruit POLK (PubMed:28297716). It promotes T-cell differentiation by destabilizing SOCS family transcripts (by similar) and suppresses type I interferon response via IFNB methylation (PubMed:30559377). METTL3 also methylates Xist RNA to facilitate random X-chromosome inactivation (PubMed:27602518), regulates cortical neurogenesis by degrading neural development transcripts (by similar), and marks pri-miRNAs for DGCR8 processing (PubMed:25799998). Independently of methyltransferase activity, it enhances translation initiation (PubMed:27117702), potentially contributing to cancer proliferation. During SARS-CoV-2 infection, viral RNA m6A modifications dampen RIGI-mediated innate immunity (PubMed:33961823).