Department of Biochemistry and Molecular Biology
University of Texas Medical Branch at Galveston
Host: Liang Tong
Title: Regulated Destabilization of Paused RNA Polymerase II: The Value of a Pair of Scissors
Abstract: The transition of RNA polymerase II (Pol II) from initiation to productive elongation is a central, regulated step in metazoan gene expression. At many genes, Pol II pauses stably in early elongation, remaining engaged with the 25-60 nucleotide-long nascent RNA for many minutes while awaiting signals for release into the gene body. However, a number of genes display highly unstable promoter Pol II, suggesting that paused polymerase might dissociate from template DNA at these promoters and release a short, non-productive mRNA. Here, we report that paused Pol II can be actively destabilized by the Integrator complex. Specifically, Integrator utilizes its RNA endonuclease activity to cleave nascent RNA and drive termination of paused Pol II. Additionally, we find that PP2A is a stable component of Integrator and is capable of dephosphorylating multiple protein targets associated with paused Pol II. These findings uncover a previously unappreciated mechanism of metazoan gene repression, akin to bacterial transcription attenuation, wherein promoter-proximal Pol II is prevented from entering productive elongation through factor-regulated termination.