The core enzyme of RNA polymerase (RNAP) in prokaryotes has five subunits and is around 400 kDa in size. It associates with the sigma initiation factor to form the RNAP holoenzyme. There are several classes of antibiotic inhibitors that target RNAP. Rifamycins and sorangicin bind near the active center and block RNA extension. Streptolydigin interacts with a target overlapping the active center and inhibits conformational cycling. Myxopyronin interacts with a target remote from the active center and interferes with opening of the cleft for DNA entry. Actinomycin binds tightly to DNA and prevents it from being used as a template.

1. Effect of inhibitors on transcription
(prokaryotes)
 Transcription
 RNA polymerase
 Inhibitors (antibiotics)

2. The core enzyme has five subunits (~400 kDa)
β': The β' subunit is the largest subunit,
encoded by the rpoC gene. The β' subunit
contains part of the active center responsible
for RNA synthesis and contains some of the
determinants for non-sequence-specific
interactions with DNA and nascent RNA
The β subunit is the second-largest subunit,
and is encoded by the rpoB gene. The β
subunit contains the rest of the active center
responsible for RNA synthesis and contains
the rest of the determinants for non-sequence-

3. αI and αII: The α subunit is the third-largest
subunit and is present in two copies per
molecule of RNAP, αI and αII.
Each α subunit contains two domains: αNTD
(N-Terminal domain) and αCTD (C-terminal
domain).
• αNTD contains determinants for assembly of
RNAP.

4. ω: The ω subunit is the smallest subunit. The
ω subunit facilitates assembly of RNAP and
stabilizes assembled RNAP.
In order to bind promoters, RNAP core
associates with the transcription initiation
factor sigma (σ) to form RNA polymerase
holoenzyme.
Sigma reduces the affinity of RNAP for
nonspecific DNA while increasing specificity
for promoters, allowing transcription to initiate
at correct sites.

7. Inhibitors (antibiotics)
(1) rifamycins and sorangicin bind near the
RNAP active center and block extension of
RNA products (binds β subunit)
(2) streptolydigin interacts with a target that
overlaps the RNAP active center and inhibits
conformational cycling of the RNAP active
center (binds β subunit)
(3) myxopyronin interacts with a target remote
from the RNAP active center and functions by
interfering with opening of the RNAP active-
center cleft to permit entry and unwinding of

8. (4) Actinomycin binds tightly to double helical
DNA structure and prevent from being
effective template for RNA synthesis