Updating the rna polymerase ctd
Although the function of the CTD remained elusive for several years after its discovery, research over the last three decades has confirmed its role as a selective and flexible scaffold for numerous factors involved in transcription (for reviews see [2, 7, 8]).
The plastic (both in terms of conformation and susceptibility to post-translational modification) and repetitive nature of the CTD allows it to undergo a relatively well-characterized sequence of phosphorylation and dephosphorylation events during the transcription cycle (initiation, elongation, and termination), linking transcription with transcription-associated processes in a temporal manner [2, 7, 9].
A particularly fascinating form of this regulation is employed during the transcription of DNA by RNA Polymerase II (RNAPII).
Eukaryotic transcription and the concomitant pre-m RNA processing require the precise coordination between, and recruitment of, specific sets of factors at specific stages of the transcription cycle.
First, although the model accounts for variations in the general phosphorylation pattern of the CTD (recognizing the presence of gene segments with high Ser5P, high Ser5/2P, and high Ser2P levels), it fails to fully capture the highly dynamic nature of the process.
The phosphorylation state of the CTD is likely to be in continuous flux throughout the entire transcription cycle, with multiple kinases and phosphatases working together to maintain specific phosphorylation patterns on particular subsets of heptads.
This coupling of transcription and associated processes has been shown to be dependent on a particular feature of RNAPII, the C-terminal repeat domain or CTD .
Distinguishing RNAPII from its prokaryotic and eukaryotic (RNAPIII and RNAPI) counterparts, the CTD is an extension of the polymerase’s largest subunit, Rpb1, and is composed of a tandem array of seven amino acid repeats with the consensus sequence Y.
Figure 1: Revised “phospho-CTD cycle.” (a) (I) For protein-coding genes, RNAPII is recruited to the promoter with an unphosphorylated CTD (IIA form); moreover, it appears that CTD phosphorylation prior to preinitiation complex (PIC) formation has an inhibitory effect on transcription.
(II) Upon preinitiation complex formation, the CTD phosphorylation of Ser5 (black) and Ser7 (red) increases.
(III) During elongation, Ser2 phosphorylation (green) increases, while Ser7 phosphorylation begins to decline, presumably due to the activity of a yet unidentified Ser7 phosphatase.
The CTD is an RNAPII-specific protein segment consisting of repeating heptads with the consensus sequence Y that has been shown to be extensively post-transcriptionally modified in a coordinated, but complicated, manner.
Since its discovery by Fischer and Krebs in 1955 , the reversible phosphorylation of proteins has been implicated in the regulation of almost every aspect of cellular function, including metabolism, cell division, differentiation, signaling, and countless others.