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:25456834, PubMed:24394384, PubMed:25569111, PubMed:28809392, PubMed:28792938, PubMed:28869969, PubMed:28965759). In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core (By similarity). 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 (By similarity). 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 (PubMed:25456834, PubMed:24394384, PubMed:25569111). 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 (PubMed:24209618). M6A also regulates circadian regulation of hepatic lipid metabolism (By similarity). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (PubMed:28809392, PubMed:28914256, PubMed:32943573). Also required for oogenesis (PubMed:32943573). 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 (By similarity). 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 (PubMed:28792938). Inhibits the type I interferon response by mediating m6A methylation of IFNB (By similarity). 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 (PubMed:28965759). M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs) (By similarity). 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 (By similarity). METTL3 mediates methylation of pri-miRNAs, marking them for recognition and processing by DGCR8 (By similarity). 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 (By similarity). an adenosine in mRNA + S-adenosyl-L-methionine = an N(6)-methyladenosine in mRNA + H(+) + S-adenosyl-L-homocysteine Methyltransferase activity is regulated by miRNAs via a sequence pairing mechanism (PubMed:25683224). Methyltransferase activity is inhibited by sumoylation (By similarity). Heterodimer; heterodimerizes with METTL14 to form an antiparallel heterodimer that constitutes an active methyltransferase (By similarity). Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:29535189, PubMed:29547716). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:29535189, PubMed:29547716). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29535189, PubMed:29547716). Interacts with NCBP1/CBP80 (By similarity). Interacts with EIF4E (By similarity). Interacts with EIF3B (By similarity). Colocalizes with speckles in interphase nuclei. Suggesting that it may be associated with nuclear pre-mRNA splicing components (PubMed:24394384). 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 site (By similarity). Present in both germ cells and somatic cells during testis development (at protein level) (PubMed:28809392). 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. Sumoylation inhibits the N6-adenosine-methyltransferase activity. Sumoylation does not affect subcellular location or interaction with METTL14. Desumoylated by SENP1. Embryonic lethality (PubMed:25569111). Blastocysts retain normal morphology and expression of pluripotency markers and yield embryonic stem cells (ESCs) at the expected ratio. However, they fail to adequately terminate their naive state and undergo aberrant and restricted lineage priming at the postimplantation stage, leading to early embryonic lethality (PubMed:25456834, PubMed:25569111). mRNAs show a nearly complete absence of N6-methyladenosine (m6A) methylation (PubMed:25456834, PubMed:25569111). RNAs show defects in splicing and adenosine to inosine editing (PubMed:25569111). Conditional knockout mice lacking Mettl3 in germ cells show male infertility caused by defects in meiosis at the zygotene stage during spermatogenesis (PubMed:28809392). Conditional knockout mice lacking Mettl3 and Mettl14 in germ cells show impaired spermatogenesis (PubMed:28914256). Conditional knockout mice lacking Mettl3 in T-cells show impaired homeostatic expansion of naive T-cells, T-cells remaining in the naive state for up to 12 weeks, thereby preventing colitis (PubMed:28792938). Naive T-cells show loss of m6A modification leading to increased Socs1, Socs3 and Cish mRNA half-life and protein levels, thereby suppressing the IL-7/STAT5 signaling pathway (PubMed:28792938). Conditional knockout mice lacking Mettl3 in the developing nervous system display protracted cell-cycle progression of cortical neural progenitor cells and reduced differentiation of radial glial cells during embryonic cortical neurogenesis (PubMed:28965759). Belongs to the MT-A70-like family. While different publications agree on the role of N6-methyladenosine (m6A) on RNA stability and its role in embryonic stem cells (ESCs) pluripotency, the precise function of Mettl3 in ESCs self-renewal is unclear. A first paper reported that Mettl3 promotes self-renewal of ESCs by maintaining the groung state of ESCs (PubMed:24394384). However, opposite conclusions were drawn by publications from other groups (PubMed:25456834, PubMed:25569111). The differences may be explained by different experimental conditions (such as cell types or RNAi off-target effects).