Poster Presentation 40th Annual Lorne Genome Conference 2019

The SPOC domain: A novel reader of the CTD code (#111)

Lisa-Marie Appel 1 , Irina Grishkovskaya 2 , Melania Bruno 1 , Aiste Kasiliauskaité 3 , Martin Puchinger 2 , Sebastian Kostrhon 1 , Richard Stefl 3 , Kristina Djinovic-Carugo 2 4 , Dea Slade 1
  1. Department of Biochemistry and Cell Biology, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
  2. Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
  3. CEITEC, Masaryk University, Brno, Czech Republic
  4. Department of Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia

The YSPTSPS heptarepeats of the C-terminal domain (CTD) of eukaryotic RNA polymerase II are differentially post-translationally modified throughout the transcription cycle. CTD-binding domains of transcription regulators and RNA processing factors recognize specific modifications, allowing their timely recruitment to the transcription machinery.

We recently identified the human protein PHF3 as a new CTD-binder involved in transcription regulation. Its SPOC domain is essential for its function and mediates the interaction with the CTD by specifically recognizing phosphorylated Serine 2 residues in two adjacent repeats. Two conserved basic patches on the surface of PHF3 SPOC anchor two phosphorylated serines, while the central patch hydrophobically stabilizes the CTD peptide. Biophysical and structural studies revealed that the CTD-binding ability is not limited to PHF3 SPOC. SPOC domains from other proteins also bind phosphorylated CTD, but with different specificity and a different mode of binding. Conserved residues contribute to the recognition of specific phosphorylation marks.

SPOC-containing proteins are involved in transcription repression and development and are often mutated in cancer. Further studies of different SPOC domains will unveil the structural determinants of their CTD-binding specificity and the functional relevance of their CTD code readout for transcription regulation.