YTHDF2

YTHDF2 is a cytoplasmic m6A reader that controls m6A-modified RNA fate through mRNA degradation and, in selected contexts, translation regulation^[1][2]. Mechanistically, YTHDF2-mediated mRNA decay targets multiple TGF-β signaling components in early postnatal mouse hippocampal neural stem cells, thereby limiting quiescence acquisition and supporting neurogenesis^[1]. In glioma models, YTHDF2 accelerates UBXN1 mRNA degradation through METTL3-mediated m6A recognition, activates NF-κB signaling, and promotes malignant progression^[3]. In glioblastoma stem cells, YTHDF2 instead stabilizes MYC and VEGFA transcripts, identifies a cancer-specific dependency, and links the YTHDF2-MYC-IGFBP3 axis to tumor growth^[2]. Compared with related YTHDF isoforms, YTHDF proteins share m6A-reader activity but display distinct cellular functions because their low-complexity N termini, post-translational modifications, subcellular localization, and partner competition differ^[4]. For experimental applications, linsitinib preferentially targeted YTHDF2-expressing glioblastoma stem cells, while a YTHDF2-specific small-molecule inhibitor suppressed tumor-cell translation and reversed paclitaxel resistance in ovarian cancer models^[2][5].