{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMETTL3 is the core catalytic subunit of the m6A RNA methyltransferase complex that installs N6‐methyladenosine modifications on a wide variety of coding and non‐coding RNAs. Detailed structural and biochemical studies have revealed that METTL3, often in a heterodimeric partnership with METTL14, adopts a conserved class I methyltransferase fold. In these complexes, METTL3 provides the catalytic activity while its partner proteins (and additional motifs) create the proper substrate‐binding interface, thereby controlling mRNA splicing, stability, and translation efficiency."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn numerous cancers, METTL3 drives oncogenic programs by enhancing the translation and stability of key mRNAs. For instance, in lung adenocarcinoma and acute myeloid leukemia, METTL3 associates with ribosomes and, independent in some cases of METTL14, promotes the translation of transcripts such as EGFR, TAZ, c‐MYC, and other critical regulators. These actions support tumor cell growth, survival, and invasiveness, underscoring its role as a pro‐tumorigenic factor in diverse malignancies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its oncogenic roles, METTL3 is also critical for proper developmental and differentiation programs. In embryonic stem cells, m6A marks orchestrate transcriptome flexibility to facilitate the exit from self‐renewal and guide lineage commitment. Similarly, in the context of circadian regulation and glioma stem‐like cell maintenance, METTL3‐mediated m6A modifications affect mRNA turnover and stability, thereby influencing cell fate decisions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMETTL3 further modulates non‐coding RNA biology by regulating the processing and maturation of microRNAs and circular RNAs. It has been shown to facilitate the maturation of oncogenic microRNAs—for example, miR‑25–3p in response to cigarette smoke in pancreatic cells and miR‑126‑5p in ovarian cancer—while also influencing back‐splicing events needed for circRNA biogenesis. Moreover, METTL3 itself can be subject to regulation by microRNAs, creating feedback loops that impact its own expression and downstream oncogenic effects."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPost‐translational modifications and stress‐related signaling pathways further fine‐tune METTL3’s activity. Its methyltransferase function can be modulated by SUMOylation and ATM‐dependent phosphorylation, which in turn affect critical cellular processes such as DNA damage repair, autophagy, and inflammatory signaling. Through stabilizing key mRNAs in signaling cascades (including those governing NF‑κB, PI3K/Akt/mTOR, and STAT pathways), METTL3 contributes not only to cancer progression but also to the modulation of antiviral responses and therapeutic sensitivity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "29"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, aberrant METTL3 expression and activity have been implicated in a broad spectrum of specific pathological conditions. In cancers such as colorectal, bladder, breast, and osteosarcoma, dysregulation of METTL3 alters key transcript levels and signaling networks (for example, via effects on the Wnt/β‑catenin or NF‑κB pathways), while in other disorders—including thyroid carcinoma, dental pulp inflammation, Alzheimer disease, and even certain viral infections—the m6A machinery plays roles that impact disease progression and therapeutic responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "30", "end_ref": "43"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these studies highlight the multifaceted roles of METTL3 in the regulation of RNA metabolism—from controlling mRNA splicing and translation to modulating non‐coding RNA processing and integrating diverse signaling pathways. 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