Abstract

uring RNA synthesis, RNA poly-merase moves erratically along DNA, frequently resting as it produces an RNA copy of the DNA sequence. Such pausing helps coordinate the appearance of a transcript with its utilization by cellular processes; to this end, the movement of RNA polymerase is modulated by mechanisms that determine its rate. For example, pausing is critical to regulatory activities of the enzyme such as the termination of transcription. It is also essential during early modifications of eu-karyotic RNA polymerase II that activate the enzyme for elongation. Two reports analyzing transcription pausing on a global scale in Escherichia coli, by Larson et al. ( 1) and by Vvedenskaya et al. ( 2) on page 1285 of this issue, suggest new functions of pausing and reveal important aspects of its molecular basis. The studies of Larson et al. and Vveden-skaya et al. follow decades of analysis of bacterial transcription that has illuminated the molecular basis of polymerase paus-ing events that serve critical regulatory functions. A transcription pause specified by the DNA sequence synchronizes the translation of RNA into protein with the transcription of leader regions of operons (groups of genes transcribed together) for amino acid biosynthesis; this coordination controls amino acid synthesis in response to amino acid availability ( 3). A protein-induced pause occurs when the E. coli ini-tiation factor σ70 restrains RNA polymerase by binding a second occurrence of the “–10” promoter element. This paused polymerase provides a structure for engaging a tran-scription antiterminator (the bacteriophage λ Q protein) ( 4) that, in turn, inhibits tran-scription pauses, including those essential for transcription termination. Knowledge about the interactions be-tween nucleic acids and RNA polymerase that induce pausing comes partly from studies on the E. coli histidine biosynthe-sis operon. RNA polymerase pauses at the leader region of this cluster of genes (the “his pause”), allowing an essential RNA hairpin structure to form just upstream of IL