Determinants for Dephosphorylation of the RNA Polymerase II C-Terminal Domain by Scp1.
Phosphorylation and dephosphorylation of the C-terminal domain (CTD) of RNA polymerase II (Pol II) represent a critical regulatory checkpoint for transcription. Transcription initiation requires Fcp1/ Scp1-mediated dephosphorylation of phospho-CTD. Fcp1 and Scp1 belong to a family of Mg(2+)-dependent phosphoserine (P.Ser)/phosphothreonine (P.Thr)-specific phosphatases. We recently showed that Scp1 is an evolutionarily conserved regulator of neuronal gene silencing. Here, we present the X-ray crystal structures of a dominant-negative form of human Scp1 (D96N mutant) bound to mono- and diphosphorylated peptides encompassing the CTD heptad repeat (Y(1)S(2)P(3)T(4)S(5)P(6)S(7)). Moreover, kinetic and thermodynamic analyses of Scp1-phospho-CTD peptide complexes support the structures determined. This combined structure-function analysis discloses the residues in Scp1 involved in CTD binding and its preferential dephosphorylation of P.Ser(5) of the CTD heptad repeat. Moreover, these results provide a template for the design of specific inhibitors of Scp1 for the study of neuronal stem cell development.[1]References
- Determinants for Dephosphorylation of the RNA Polymerase II C-Terminal Domain by Scp1. Zhang, Y., Kim, Y., Genoud, N., Gao, J., Kelly, J.W., Pfaff, S.L., Gill, G.N., Dixon, J.E., Noel, J.P. Mol. Cell (2006) [Pubmed]
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