INHIBITORS OF TRANSCRIPTION SUCH AS 5,6-DICHLORO-1-BETA-D-RIBOFURANOSYLBENZIMIDAZOLE AND ISOQUINOLINE SULFONAMIDE DERIVATIVES (H-8 AND H-7-ASTERISK) PROMOTE DEPHOSPHORYLATION OF THE CARBOXYL-TERMINAL DOMAIN OFRNA-POLYMERASE-II LARGEST SUBUNIT
Mf. Dubois et al., INHIBITORS OF TRANSCRIPTION SUCH AS 5,6-DICHLORO-1-BETA-D-RIBOFURANOSYLBENZIMIDAZOLE AND ISOQUINOLINE SULFONAMIDE DERIVATIVES (H-8 AND H-7-ASTERISK) PROMOTE DEPHOSPHORYLATION OF THE CARBOXYL-TERMINAL DOMAIN OFRNA-POLYMERASE-II LARGEST SUBUNIT, The Journal of biological chemistry, 269(18), 1994, pp. 13331-13336
The RNA polymerases IIO and IIA differ by the extent of phosphorylatio
n in the carboxyl-terminal domain (CTD) of the largest subunit. It has
been proposed that the IIA form of RNA polymerase II interacts with t
he promoter to form a stable preinitiation complex whereas the IIO for
m would be generated upon entry into initiation of transcription. Phos
phorylation of the CTD might be required to release the interaction be
tween the polymerase and the promoter binding factors. In this paper,
we show that in the presence of actinomycin D, the phosphorylated IIO
form accumulates. In contrast, the dephosphorylated IIA form accumulat
es while the amount of phosphorylated IIo form decreases in cells trea
ted with CTD-kinase inhibitors such as the nucleoside analog, 5,6-dich
loro-1-beta-D-ribofuranosylbenzimidazole or the isoquinoline sulfonami
de derivatives H-7 or H-8. These changes are fast and suggest a very
rapid phosphate turnover on the CTD. Transcription is inhibited in int
act cells by drug concentrations that are effective in altering CTD ph
osphorylation, although no causal relationship is established yet. The
se effects do not concern other cellular functions such as protein syn
thesis, Thus isoquinoline sulfonamide derivatives might be helpful to
further dissect the role of CTD phosphorylation in transcription.