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J Mol Biol. 2019 May 30. pii: S0022-2836(19)30326-2. doi: 10.1016/j.jmb.2019.05.042. [Epub ahead of print]

The mechanisms of substrate selection, catalysis and translocation by the elongating RNA polymerase.

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Department of Biochemistry, University of Turku, Turku, Finland.
Department of Microbiology and The Center for RNA Biology, The Ohio State University, Columbus, OH, USA. Electronic address:


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, RNAP selects a correct substrate, adds it to a growing chain, and moves one nucleotide forward before repeating the cycle. Yet 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.


RNA polymerase; proofreading; transcription elongation; translocation; trigger loop


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