RNA Polymerase Pauses Precisely and Regulates Gene Expression

RNA polymerase pausing is a key regulatory step in transcription. Here, we isolated nascent RNA with actively transcribing RNA polymerase, then mapped the locations of the polymerase in cells from different individuals and cell types. We found paused RNA polymerases in over 7,000 human genes. RNA polymerase pausing is highly consistent across individuals and cell types. At nearly 2,000 sites, RNA polymerases paused at the same nucleotide locations. These precise pause sites are marked by DSIF complexes and a sequence motif where cytosine is the pause base at over 65% of the sites. Genes with paused polymerase have lower expression levels. Population data show that these expression levels can be increased by changing the pause base from a cytosine to another base. Thus, these findings on the cis- and trans-acting elements that regulate pausing can be leveraged for expression-based therapeutics.