YTHDF1 functions as a non-canonical nuclear checkpoint that couples R-loop homeostasis to innate immune restraint and adaptive immune resistance in cancer（CUT&Tag）

YTHDF1 is an mRNA-binding protein previously characterized as a cytoplasmic m⁶A reader. Emerging evidence indicates that YTHDF1 also functions in the nucleus, where it associates with chromatin and contributes to the regulation of R-loop homeostasis.

Loss of YTHDF1 results in R-loop accumulation, genomic instability, cytosolic DNA release, and activation of the cGAS–STING–type I interferon pathway. Mechanistically, YTHDF1 interacts with the chromatin remodeler ARID1A at immune-associated genomic regions, suggesting a cooperative role in maintaining genome stability and regulating immune-related transcriptional programs. To investigate the transcriptomic and chromatin-level consequences of YTHDF1 and ARID1A perturbation, we generated RNA sequencing (RNA-seq) and R-loop CUT&Tag datasets in A549 human lung cancer cells.