DGCR8 promotes RNA polymerase II pause release independently of DROSHA [ChIP-seq]

Whether DGCR8 also exerts a direct, microprocessor independent function in the RNA polymerase II (Pol II) transcription cycle remains unclear. Here, we combined rapid, acute protein depletion with nascent transcription profiling and uncovered a non-canonical role for DGCR8 in transcriptional control in mouse embryonic stem cells (mESCs).

We found that DGCR8 broadly occupies promoters and transcription start sites (TSSs) with limited co occupancy by its catalytic microprocessor partner DROSHA. Acute DGCR8 depletion triggers an immediate, genome wide reduction in nascent RNA synthesis that is not phenocopied by acute DROSHA depletion. Mechanistically, DGCR8 loss decreases Pol II engagement at promoters and induces a pervasive blockade in promoter proximal pause release, indicating a direct requirement for DGCR8 in the transition to productive elongation.