Regulation of transcription through the RNA polymerase secondary channel

Irina Artsimovitch

http://www.osumicrobiology.org/faculty/iartsimovitch.htm

The Ohio State University

Bacterial RNA polymerase serves as a target for numerous regulatory factors that modulate gene expression and 
antibiotics that inhibit transcription. The RNA polymerase secondary channel serves as a major recruitment site
 for a diverse group of transcription regulators.  This channel has been originally proposed to serve 
as an entryway for the incoming NTP substrates and likely accommodates the 3' end of the nascent RNA that 
is threaded through the active site during transcriptional arrest. The secondary channel leads straight
 to the enzyme active site, allowing the accessory proteins (DksA, GreA, GreB, Gfh1)
 and antibiotics (microcin J25 and tagetitoxin) to directly alter the catalytic properties of RNA polymerase. 
Bacterial proteins that act through the secondary channel all contain a long coiled-coil domain,
 which extends into the secondary channel and coordinates the catalytic or inhibitory Mg2+ ions 
in vicinity of the active site using the acidic residues located within a short linker at the coiled-coil tip. 
Although the coiled-coil domains are structurally superimposable, neither the sequence nor the effects 
of these proteins on transcription are necessarily similar. Strikingly, this functional diversity 
is achieved through subtle variations in the conformation and sequence of just a few residues within the linker.