PCF11 is a critical component of the pre-mRNA cleavage and polyadenylation complex that plays essential roles in RNA polymerase II transcription termination and mRNA 3'-end processing 1. As a scaffold protein, PCF11 facilitates transcription termination by directly binding to the RNA polymerase II C-terminal domain and promoting dissociation of elongating polymerase from DNA 2. PCF11 functions in collaboration with other factors including SPT6 and PNUTS to regulate transcription termination at both gene ends 3. The protein exhibits dual regulatory functions depending on gene architecture: it enhances termination of short genes while suppressing intronic polyadenylation in long genes, thereby modulating gene expression based on gene size 4. PCF11 serves as a specific reader for the m6Am RNA modification, where m6Am sequesters PCF11 away from RNA polymerase II to suppress premature termination 5. In disease contexts, PCF11 regulation is crucial for neuroblastoma differentiation, where downregulation promotes neurodifferentiation programs and associates with favorable outcomes 6. PCF11's autoregulatory mechanisms maintain homeostasis of polyadenylation site usage, and its dysregulation contributes to cancer vulnerabilities through altered intron retention patterns 7.