The carboxy-terminal domain of RNA polymerase II large subunit: simple repeats are not simple

Transcription, as a crucial step in the transmission of genetic information, is completed by DNA-dependent RNA polymerase. In eukaryotes, the transcription of protein-coding genes is completed by RNA polymerase II (Pol II). A distinctive feature of Pol II is the carboxy-terminal domain (CTD) of its largest subunit, RPB1, which is composed of a series of heptapeptide repeats that play a vital role in transcription. Here, we provide a comprehensive review and summary of the sequence characteristics and evolutionary trajectory of the eukaryotic RPB1 CTD, as well as its regulatory function within the transcription cycle. We particularly focus on the mechanisms by which the CTD participates in the regulation of transcription and co-transcriptional processing through post-translational modifications. This deepens our understanding of the intricate regulatory mechanisms governing gene transcription in eukaryotes and lays the groundwork for further investigation into the role of the RPB1 CTD.