Applying the brakes to transcription: regulation of gene expression by RNA polymerase pausing

Transcription by RNA polymerase is punctuated by transient pausing events. Pausing provides additional time for proper RNA folding and binding of regulatory factors to the paused transcription elongation complex or the nascent RNA. Depending on the organism and the genomic context, the general transcription elongation factors NusA and NusG stimulate or suppress pausing. Both Escherichia coli and Bacillus subtilis NusA stimulate pausing in vitro, while the genome-wide role of NusA on pausing has only been examined in B. subtilis. NusG-dependent pausing was identified throughout the B. subtilis genome, and in several instances, these pauses were shown to regulate the expression of the downstream gene(s). This pro-pausing activity was also observed for Mycobacterium tuberculosis NusG. In contrast, E. coli NusG functions as an anti-pausing factor by suppressing pausing throughout the genome. These differences in the function of NusG highlight the importance of studying fundamental processes in a variety of bacterial species. This review will highlight recent advances gained by the ability to identify pauses genome-wide that are either stimulated or suppressed by these two conserved transcription elongation factors.