ARF alters PAF1 complex integrity to selectively repress oncogenic transcription programs upon p53 loss. ARF alters PAF1 complex integrity to selectively repress oncogenic transcription programs upon p53 loss

In this study, we found that the ARF tumor suppressor directly binds the PAF1 subunit to block the assembly of PAF1 complex (PAF1c) and its interaction with RNAPII, thereby dampening PAF1c-dependent transcription in vitro and in cells. Using RNA-seq of control (shNT) and ARF knockdown (shARF) mouse embryonic fibroblasts (MEFs) we first define transcriptome changes upon ARF loss. Through downstream mechanistic analysis we then validate direct ARF-mediated inactivation of PAF1c-dependent RNAPII transcription and their cellular consequences. Overall design: Comparative gene expression profiling analysis of RNA-seq data for ARF (shARF) and control knockdown (shNT) MEFs.