The largest subunit of human RNA Polymerase
II contains highly flexible C-terminal domain (CTD) that is composed of 52
heptapeptide repeats (approximately first half of the CTD consists of consensus
heptapeptide repeats, YSPTSPS, while the second half is sequentially
divergent). Several CTD’s canonical and non-canonical residues can be subjects
of post-translational modifications. Tyrosine, threonine, and serine residues
undergo dynamic phosphorylation/dephosphorylation resulting in specific
phosphorylation patterns throughout different stages of transcription cycle.
These phosphorylation patterns are recognized by various transcription and
processing factors during the transcription cycle. Therefore, CTD plays an
important role in the regulation of transcription and coupling of transcription
to post-transcriptional processes such as mRNA processing.
In this work, we show that human
transcription factor, RPRD2, recognizes specifically pSer2 or pThr4
phosphorylated forms of CTD via its CTD-interacting domain (CID) in a similar
way to its yeast homologue, Rtt103. The interaction of RPRD2 CID with pSer2
phosphorylated CTD is further enhanced by additional phosphorylation on pSer7.
To provide mechanistic details of the interaction between RPRD2 CID and pSer2,7
CTD, the solution structure was obtained using NMR spectroscopy. pSer2 and
pThr4 phosphomarks occur mainly during the late elongation and termination.
RPRD2s preference
for these two phosphomarks suggests possible involvement of RPRD2 in
transcription termination.