Promoter-proximal Pol II: when stalling speeds things up.

Expression of genes was long thought to be regulated primarily at the level of RNA polymerase II (Pol II) recruitment to a gene promoter, and the dozen genes that did not fit this paradigm were regarded as exceptions. However, recent analyses of genome-wide Pol II distribution in Drosophila and mammalian systems have indicated that a large number of genes might be regulated at a step subsequent to Pol II recruitment, during early transcription elongation. At these genes, Pol II begins transcription but stalls after synthesizing a short RNA, and it is the release of this engaged Pol II from the promoter-proximal region that is rate limiting for transcription. Notably, promoter-proximal Pol II stalling is prevalent at genes involved in development and response to stimuli, suggesting that Pol II stalling during early elongation plays important roles in rapid and precise control of gene expression. Here we briefly summarize the current data on promoter-proximal Pol II stalling and discuss implications of this newly appreciated regulatory strategy.