This research article introduces a high-throughput epitranscriptomic screening platform designed to identify functional m6A RNA modifications that drive cancer progression. By utilizing a Cas13-directed methyltransferase system, the researchers mapped the functional landscape of these modifications in prostate and lung cancer models, uncovering over 200 sites that regulate cell growth. A primary discovery identifies CHD9 as a critical tumor-suppressive gene whose protein levels are enhanced by m6A deposition at a specific site. Mechanistically, the study reveals that m6A readers YTHDF1 and YTHDF3 promote the translation of CHD9, which subsequently anchors the protein MYBBP1A in the nucleoplasm to activate p21-mediated growth arrest. Ultimately, this work provides a scalable framework for systematic RNA-level editing and highlights a novel regulatory axis for controlling tumor suppression.

References:

• Xu X, Wang Y, Zhu H, et al. METTL3-based epitranscriptomic editing screening identifies functional m6A sites in cancers[J]. Nature Cancer, 2026: 1-15.