Phosphoserines of the Carboxy Terminal Domain of RNA Polymerase II Are Involved in the Interaction with Transcription-Associated Proteins (TAPs)

Abstract

Generation of productive transcripts of protein coding genes in eukaryotes is a complex, multistep process centrally controlled by the RNA polymerase II (Pol II) complex. The carboxy terminal domain (CTD) of the largest subunit of the enzyme is designed to be modified by differential phosphorylation, and plays a key role in orchestrating the multiple events of the process by interacting with a host of transcription-associated proteins (TAPs) at different stages. We analyzed, in silico, the role of serine phosphorylation of CTD in relation to molecular interaction between different TAPs and a representative part of the CTD repeat structure. Using molecular docking, we investigated eight different proteins involved in capping, elongation, splicing, 3' end cleavage, or polyadenylation functions during the transcription process. Among the different phosphorylated forms of CTD, the form found to have the most affinity for a particular protein was also the form that is predominant during that process, the only exception being the equally high affinity of S2PCTD to Spt4, although S5PCTD is the known active form during elongation. The unique phosphoserine of the CTD forms associated with the TAPs was an important participant in the association between both the molecules. These studies have also identified other residues of TAPs interacting with CTD which in previous studies have not been recognized as being functionally significant. These findings add to an emerging body of literature on the regulatory aspects of genomics and proteomics and thus, might catalyze future applications for discovery and translational omics science.