A central, previously unknown role of the PNUTS complex in gene transcription depending on RNA polymerase II has been uncovered. According to a study published in Molecular Cell, the PNUTS complex controls transcriptional pause release and resumption of elongation via a mechanism that is essential for controlling gene expression. PNUTS (protein phosphatase 1 nuclear targeting subunit) is an enzyme encoded by the gene PPP1R10 (PNUTS) and regulates the activity of protein phosphatase 1 (PP1). Until now, it was only known that the complex consisting of PNUTS, PP1 and other proteins is essential for transcription termination.

The highly regulated process of gene transcription roughly takes place in three major phases: initiation, elongation and termination. During elongation, RNA polymerase II (RNAP II) moves along the DNA and copies it into a complementary mRNA strand, serving as a template for the production of proteins. However, this copying process repeatedly comes to a standstill, with RNAP II pausing. By mouse experiments and using imaging, biochemical and quantitative genomic and proteomic methods, the researchers have now discovered that the PNUTS complex is responsible for RNAP II pause release. To do this, PNUTS interacts with PP1. The study showed that PNUTS recognizes factors required for promoting pause release and elongation and enables their dephosphorylation by PP1.