Accepted: 08/03/12

helmholtz-muenchen.de Eukaryotic RNA polymerase II (RNAP II) has evolved an array of heptad repeats with the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 at the carboxy-terminal domain (CTD) of its largest subunit (Rpb1). Dynamic phosphorylation of Ser2, Ser5 and Ser7 residues orchestrates the binding of transcription and RNA processing factors to the transcription machinery. Recent studies show that the two remaining potential phosphoryla-tion sites, tyrosine-1 and threonine-4, are phosphorylated as well and contrib-ute to the previously proposed “CTD code”. With the impairment of binding of CTD interacting factors, these novel phosphorylation marks add an accessory layer of regulation to the RNAP II tran-scription cycle. In eukaryotes three different DNA dependent RNA polymerases convert the information encoded in the chro-matin template into RNA. RNAP I transcribes rDNA in rRNA, RNAP II transcribes all protein encoding genes in mRNA as well as small, non-coding RNAs like snRNAs, snoRNAs and miR-NAs. RNAP III transcribes various short genes, which are coding for structural or catalytic RNAs like tRNAs, 5S rRNA or the U6 snRNA. All three enzymes are composed of sev-eral subunits and have large similarities but show also clear structural differences in their periphery.1 The most eye-catch-ing difference, which separates RNAP II from its relatives, is the carboxy-terminal domain (CTD) of its largest subuni