YTHDC1

YTHDC1 is a nuclear m⁶A RNA reader that selectively binds m⁶A-containing RNA through its YTH domain and preferentially recognizes GG(m⁶A)C sequences^[1]. Mechanistically, YTHDC1 controls nuclear RNA metabolism by promoting mRNA splicing and by mediating export of methylated mRNAs from the nucleus to the cytoplasm through SRSF3 and NXF1^[2][3]. In AML models, YTHDC1 supports leukemia cell proliferation, survival, AML development, and leukemia stem cell self-renewal through an MCM4 DNA-replication mechanism^[4]. Compared with related isoforms, YTHDC1 functions as the only nuclear YTH-family m⁶A-binding protein in this export pathway, whereas YTHDF2 mainly mediates cytoplasmic decay of methylated mRNAs and YTHDC2 has RNA helicase activity essential for mammalian germline meiosis^[2][5]. For experimental applications, early YTHDC1 inhibitors that occupy the RNA-binding pocket disrupt YTHDC1-m⁶A RNA interaction, dissolve YTHDC1 condensates, and suppress oncogenic gene expression in AML cell lines^[6].

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