YTHDC2

YTHDC2 (YTH N6-methyladenosine RNA binding protein 2) is a multifunctional m⁶A reader and 3′→5′ RNA helicase that regulates post-transcriptional gene expression through RNA binding, ATP-dependent helicase activity, and interactions with RNA decay machinery^[1][2]. YTHDC2 recognizes m⁶A-modified transcripts and contributes to the control of RNA stability, translation, and transcriptome remodeling, thereby supporting developmental and cellular differentiation programs^[1][3]. Mechanistically, YTHDC2 functions as an RNA-induced ATPase with 3′→5′ helicase activity and can recruit the 5′→3′ exoribonuclease XRN1 through its ankyrin-repeat region, linking RNA recognition to RNA turnover pathways^[1]. A central biological role of YTHDC2 is the regulation of the transition from mitotic to meiotic gene expression programs, where it acts together with MEIOC and is required for successful meiotic progression and fertility in mammalian germ cells^[2][4]. Consistent with this function, genetic disruption of YTHDC2 causes defects in meiosis and fertility, while pathogenic variants have been associated with human primary ovarian insufficiency^[4][5]. Beyond germline biology, altered YTHDC2 expression has been linked to multiple cancers, including head and neck squamous cell carcinoma and colorectal cancer, where reduced expression correlates with unfavorable clinical outcomes^[6][7]. Compared with other YTH-domain family members, YTHDC2 uniquely combines an m⁶A-binding YTH domain with an RNA helicase core and exhibits relatively weak m⁶A-dependent transcript recognition, suggesting functional specialization distinct from canonical YTH readers^[3]. No widely established selective agonists or inhibitors of YTHDC2 have been reported in the cited literature, and current research primarily relies on genetic and molecular perturbation models to investigate its biological functions^[2][4].

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