Updating the RNA polymerase CTD code: adding gene-specific layers

The carboxyl-terminal domain (CTD) of RNA polymerase (pol) II comprises multiple tandem repeats with the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 that can be extensively and reversibly modified in vivo. CTD modifications orchestrate the interplay between transcription and processing of mRNA. Although phosphorylation of Ser2 (Ser2P) and Ser5 (Ser5P) residues has been described as being essential for the expression of most pol II-transcribed genes, recent findings highlight gene-specific effects of newly discovered CTD modifications. Here, we incorporate these latest findings in an updated review of the currently known elements that contribute to the CTD code and how it is recognized by proteins involved in transcription and RNA maturation. As modification of the CTD has a major impact on gene expression, a better understanding of the CTD code is integral to the understanding of how gene expression is regulated.