Article

Transcribing RNA polymerase II is phosphorylated at CTD residue serine-7

Institute of Clinical Molecular Biology and Tumour Genetics, GSF-Research Center of Environment and Health, Munich Center for Integrated Protein Science (CiPSM), Marchioninistrasse 25, 81377 Munich, Germany.
Science (Impact Factor: 33.61). 01/2008; 318(5857):1780-2. DOI: 10.1126/science.1145977
Source: PubMed

ABSTRACT

RNA polymerase II is distinguished by its large carboxyl-terminal repeat domain (CTD), composed of repeats of the consensus
heptapeptide Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. Differential phosphorylation of serine-2 and serine-5 at the 5′ and 3′ regions of genes appears to coordinate the localization
of transcription and RNA processing factors to the elongating polymerase complex. Using monoclonal antibodies, we reveal serine-7
phosphorylation on transcribed genes. This position does not appear to be phosphorylated in CTDs of less than 20 consensus
repeats. The position of repeats where serine-7 is substituted influenced the appearance of distinct phosphorylated forms,
suggesting functional differences between CTD regions. Our results indicate that restriction of serine-7 epitopes to the Linker-proximal
region limits CTD phosphorylation patterns and is a requirement for optimal gene expression.

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    • "The DYRK1A preference for Ser2p and Ser5p is in agreement with DYRK1A favoring Pro residues at the +1 position of its phosphorylation motif (Himpel et al., 2000). Notably, the DYRK1A-phosphorylated CTD was also detected with the H5 antibody (Figure S6E), which has greater affinity for CTD phosphorylated at both Ser2 and Ser5 rather than Ser2 alone (Chapman et al., 2007), suggesting that DYRK1A could phosphorylate both residues within the same repeat, at least in vitro. Moreover, the large band shift observed upon phosphorylation indicates that DYRK1A can phosphorylate several of the hepta-repeats in the same molecule, as it has been described for the CTD kinase CDK9 (Czudnochowski et al., 2012). "
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