PT - JOURNAL ARTICLE AU - Feiyue Lu AU - Bede Portz AU - David S. Gilmour TI - Interplay between consensus and divergent RNA polymerase II C-terminal domain repeats in viability and targeting AID - 10.1101/448506 DP - 2018 Jan 01 TA - bioRxiv PG - 448506 4099 - http://biorxiv.org/content/early/2018/10/21/448506.short 4100 - http://biorxiv.org/content/early/2018/10/21/448506.full AB - The carboxy-terminal domain (CTD) of RNA polymerase II (Pol II) is composed of repeats of the consensus YSPTSPS, and is an essential binding scaffold for transcription-associated factors. Metazoan CTDs have well-conserved lengths and sequence compositions arising from the evolution of divergent motifs, features thought to be essential for development. To the contrary, we show that a truncated CTD composed solely of YSPTSPS repeats fully supports Drosophila viability, but a CTD with enough YSPTSPS repeats to match the length of the wild-type Drosophila CTD is defective. Furthermore, a fluorescently-tagged CTD lacking the rest of Pol II dynamically enters transcription compartments, indicating that the CTD functions as a signal sequence. However, CTDs with too many YSPTSPS repeats are more prone to localize to static nuclear foci independent of the chromosomes. We propose that the sequence complexity of the CTD offsets aberrant behavior caused by excessive repetitive sequences without compromising its targeting function.