N6-methyladenosine reader protein (m6A reader)

N6-methyladenosine (m6A) reader proteins are a diverse group of RNA-binding proteins that specifically recognize and bind to the m6A modification, the most abundant internal modification in eukaryotic mRNA (NIH, 2021). These proteins, including the YTH domain family (YTHDF1-3, YTHDC1-2), IGF2BPs, and HNRNPs, act as the primary effectors of the epitranscriptomic code by translating the m6A mark into functional outcomes such as mRNA degradation, translation enhancement, or alternative splicing (Frontiers in Oncology, 2023). By controlling the metabolic fate of thousands of transcripts, m6A readers play essential roles in fundamental biological processes, including cell differentiation, embryonic development, and immune response regulation (NIH, 2021). In disease contexts, particularly oncology, m6A readers are frequently dysregulated and function as oncogenic drivers by stabilizing or promoting the translation of pro-survival and metastatic mRNAs (ResearchGate, 2023). For example, YTHDF1 and YTHDF2 are often overexpressed in various solid tumors and leukemias, where they contribute to tumor growth, drug resistance, and immune evasion (NIH, 2021). Consequently, these proteins have emerged as promising therapeutic targets, with small-molecule inhibitors like SKLB-Y13 and YTH-IN-1 being developed to disrupt their m6A-binding pockets (MedChemExpress, 2024). However, therapeutic development must address challenges such as the functional redundancy among reader proteins and the potential for toxicity in normal tissues where m6A signaling is critical for homeostasis (NIH, 2022).

Other names

m6A-binding proteinYT521-B homology domain-containing proteinYTH domain-containing proteinIGF2BPHNRNPEpitranscriptomic reader

Competitive inhibition of the m6A-binding pocket to disrupt the interaction between the reader protein and m6A-modified RNA transcripts.