RNA polymerase II removal: transcription quality control and gene regulation

At the heart of the central dogma is the synthesis of RNA from a DNA template. In eukaryotes, this process is carried out by three RNA Polymerases - Pol I, II and III. While Pol I and Pol III are dedicated to producing rRNAs and tRNAs, it is Pol II that drives the complexity of eukaryotic life, transcribing all protein-coding genes and thousands of non-coding RNA loci in a context-specific manner. As such, Pol II faces specific challenges: it must traverse tens to thousands of kilobases of DNA, overcome any obstacles along the way and associate with the correct regulatory factors at the correct time and place. What happens if any of this goes wrong? Over the last couple of years, we learned that Pol II molecules unable to overcome these challenges are removed from genes. Moreover, cells also use eviction and destruction of the Pol II apparatus to regulate gene expression. Strikingly, some studies estimate the fate of at least 80% of Pol II molecules is to be removed from genes rather than to complete transcription. This Review will summarize recent discoveries of pathways that clear Pol II at different stages of the transcription cycle.