Ready, pause, go: regulation of RNA polymerase II pausing and release by cellular signaling pathways

•Pol II pausing is a rate-limiting step in the transcription of many metazoan genes.•Pol II pausing can be regulated by cellular signaling pathways.•Pol II pausing and/or release can be regulated as an endpoint of signaling pathways.•Regulation of Pol II pausing and release allows fine-tuning of gene expression.

Promoter-proximal pausing by RNA polymerase II (Pol II) is a well-established mechanism to control the timing, rate, and possibly the magnitude of transcriptional responses. Recent studies have shown that cellular signaling pathways can regulate gene transcription and signaling outcomes by controlling Pol II pausing in a wide array of biological systems. Identification of the proteins and small molecules that affect the establishment and release of paused Pol II is shedding new light on the mechanisms and biology of Pol II pausing. This review focuses on the interplay between cellular signaling pathways and Pol II pausing during normal development and under disease conditions.