YTHDF3

YTHDF3 (YTH N6-methyladenosine RNA binding protein 3) is a cytoplasmic m⁶A reader that recognizes methylated transcripts and functions as a key regulator of post-transcriptional RNA metabolism, linking mRNA translation and decay through coordinated interactions with other YTH domain family proteins^[1][2]. Mechanistically, YTHDF3 promotes protein synthesis by cooperating with YTHDF1 and facilitates the turnover of methylated transcripts through YTHDF2-dependent decay pathways, thereby accelerating the metabolism of m⁶A-modified mRNAs in the cytoplasm^[1][2]. This integrated regulatory network positions YTHDF3 as an important component of m⁶A-mediated gene-expression control and cellular adaptation processes^[1][2]. In experimental models, YTHDF3 has been shown to promote autophagy under nutrient-deficient conditions by recognizing m⁶A-modified FOXO3 transcripts and enhancing their translation through recruitment of translation-initiation factors, linking epitranscriptomic regulation to metabolic homeostasis^[3]. Disease-related studies further demonstrate that YTHDF3 contributes to cancer progression, including breast cancer brain metastasis, where it enhances the translation of m⁶A-enriched metastasis-associated transcripts and supports multiple steps of metastatic colonization^[4]. Compared with related isoforms, YTHDF1 primarily enhances translation whereas YTHDF2 predominantly promotes mRNA degradation; YTHDF3 is distinguished by its coordinating role that connects these processes and fine-tunes transcript fate within the m⁶A regulatory network^[1][2]. Currently, specific YTHDF3-targeted agonists or inhibitors remain insufficiently established for routine research applications in the cited literature^[1-4].