RNA polymerase II (Pol II) is responsible for the synthesis of all messenger RNA and most small nuclear RNA and microRNA in eukaryotic cells. It is subject to complex regulation, some of which impinges on the C-terminal domain (CTD) of the largest subunit of the polymerase complex. This contains 52 heptapeptide (seven amino acid) repeats in humans. This domain is essential for Pol II activity. Sawicka et al. addressed the paradox of variation in the frequency and number of repeats among species by looking at transcriptional output in human cells with only 25 repeats. The authors found that cells with half the number of repeats were fine in a static state but responded poorly to growth stimulation. This indicates that full-length CTD is required to mediate interactions between proximal and distant elements in gene loci.

EMBO J. 8, e107015 (2021).