Abstract
Accurate gene transcription in eukaryotes depends on isomerization of serine-proline bonds within the carboxy-terminal domain (CTD) of RNA polymerase II. Isomerization is part of the “CTD code” that regulates recruitment of proteins required for transcription and co-transcriptional RNA processing. Saccharomyces cerevisiae Ess1 and its human ortholog, Pin1, are prolyl isomerases that engage the long heptad repeat (YSPTSPS)26 of the CTD by an unknown mechanism. Here, we used an integrative structural approach to decipher Ess1 interactions with the CTD. Ess1 has a rigid linker between its WW and catalytic domains that enforces a distance constraint for bivalent interaction with the ends of long CTD substrates (≥4–5 heptad repeats). Our binding results suggest that the Ess1 WW domain anchors the proximal end of the CTD substrate during isomerization, and that linker divergence may underlie evolution of substrate specificity.
Highlights
Accurate gene transcription in eukaryotes depends on isomerization of serine-proline bonds within the carboxy-terminal domain (CTD) of RNA polymerase II
S. cerevisiae Ess[1] was co-crystallized with a single heptad repeat (1R) phospho-Ser[5] CTD peptide and the X-ray structure was determined at 2.4 Å resolution (Fig. 1a, Table 1)
A peak of positive electron density in the WW domain near W38 and Y27 (Fig. S2a) was observed that we interpret as the position of proline 6 of the heptad repeat, as observed in the Pin1-CTD structure[23]
Summary
Accurate gene transcription in eukaryotes depends on isomerization of serine-proline bonds within the carboxy-terminal domain (CTD) of RNA polymerase II. Saccharomyces cerevisiae Ess[1] and its human ortholog, Pin[1], are prolyl isomerases that engage the long heptad repeat (YSPTSPS)[26] of the CTD by an unknown mechanism. Ess[1] is highly conserved among eukaryotes[1,2,3] and plays a key role in transcription by regulating the activity of RNA polymerase II (RNAPII)[1]. Ess[1] binds to RNAPII to carry out its function is not well understood It is not known how Ess[1] engages the long unstructured carboxy-terminal domain (CTD) of Rpb[1], the largest subunit of RNAPII. Phosphorylation of Ser[2] or
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