RPB1

RPB1 is the largest subunit of RNA polymerase II, the enzyme responsible for transcribing mRNA and many noncoding RNAs in eukaryotic cells. In humans it is encoded by the POLR2A gene and is essential for cell viability. RPB1, together with other subunits, forms the catalytic core of RNA polymerase II and participates in promoter passage, DNA template handling, transcription elongation, and coordination with RNA processing.

Structure of RPB1 features an N-terminal domain that contributes to the core polymerase framework and a long C-terminal domain (CTD). The CTD consists of multiple tandem repeats of the heptad sequence YSPTSPS; in humans there are 52 repeats, while many yeasts possess fewer (about 26). The CTD is intrinsically flexible and serves as a dynamic platform for the assembly of RNA processing factors during transcription.

Function and CTD regulation: The CTD acts as a scaffold that recruits capping enzymes, splicing factors, and 3′-end processing factors to the transcription machinery, enabling coupling of transcription to RNA maturation. Phosphorylation of the CTD regulates the transition from initiation to elongation and the recruitment of processing factors. Ser5 phosphorylation by CDK7 (part of TFIIH) promotes promoter escape and capping, whereas Ser2 phosphorylation by CDK9 (P-TEFb) facilitates productive elongation. Ser7 phosphorylation also occurs and has roles in certain RNA processing steps. Dephosphorylation by phosphatases such as FCP1 resets the CTD between cycles.

Clinical and research notes: Given its essential role, POLR2A/RPB1 is highly conserved across eukaryotes. Alterations in POLR2A expression or CTD regulation have been observed in cancer genomics studies and are of interest in transcriptional regulation research. See also RNA polymerase II, transcription, and C-terminal domain.