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Inhibiting factor

SBKB [doi:10.1038/sbkb.2011.03]
Featured Article - February 2011
Short description: Transcription initiation and elongation by RNA polymerase is inhibited by GreA. A recent crystal structure reveals the mechanism.

Image courtesy of Shigeyuki Yokoyama.

RNA polymerase (RNAP) is the main enzyme responsible for transcription. It synthesizes RNA that is complementary to the DNA target strand, and its action are tightly regulated by transcription factors such as the bacterial protein GreA or its Thermus thermophilus homolog Gfh1, which inhibit transcription initiation and elongation.

Previously solved structures of RNAP in the absence of transcription factors show a crab’s claw appearance, with four separate modules—the core, shelf, clamp and jaw-lobe—that are able to move relative to each other. Between the two central modules, the core and the shelf, lies the entry point of nucleotide triphosphates (NTPs) into the catalytic site.

When Gfh1 is added to RNAP, transcription is inhibited in a process whose exact mechanism has not been clear. Now Yokoyama and colleagues have revealed the structure of Gfh1 bound to RNAP in the presence of DNA and RNA. In the structure, the four-module architecture of RNAP is retained, but the two central modules are rotated into a ‘ratcheted’ orientation by 7 degrees relative to their positions in the previous transcription elongation complex or apo holoenzyme structures.

This has the effect of opening up the nucleic acid binding channel. At the same time, the N-terminal coiled coil of Gfh1 blocks the NTP entry channel between the two central modules, with the tip of the coiled coil located within the phosphate-binding site. This structure shows that Gfh1 works by stopping NTP from binding to RNAP and holding RNAP in a ratcheted state, which perhaps might be useful for other transcription steps.

Maria Hodges


  1. S. Tagami et al. Crystal structure of bacterial RNA polymerase bound with a transcription inhibitor protein.
    Nature 468, 978-982 (2010). doi:10.1038/nature09573

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