Multi-subunit DNA-dependent RNA polymerases synthesize all classes of
cellular RNAs, ranging from short regulatory transcripts to gigantic
messenger RNAs. RNA polymerase has to make each RNA product in just one
try, even if it takes millions of successive nucleotide addition steps.
During each step, RNA polymerase selects a correct substrate, adds it to
a growing chain, and moves one nucleotide forward before repeating the
cycle. However, RNA synthesis is anything but monotonous: RNA polymerase
frequently pauses upon encountering mechanical, chemical and torsional
barriers, sometimes stepping back and cleaving off nucleotides from the
growing RNA chain. A picture in which these intermittent dynamics enable
processive, accurate, and controllable RNA synthesis is emerging from
complementary structural, biochemical, computational, and
single-molecule studies. Here, we summarize our current understanding of
the mechanism and regulation of the on-pathway transcription
elongation. We review the details of substrate selection, catalysis,
proofreading, and translocation, focusing on rate-limiting steps,
structural elements that modulate them, and accessory proteins that
appear to control RNA polymerase translocation.