A 10 residue motif at the C-terminus of the RNA pol II CTD is required for transcription, splicing and 3' end processing

Abstract
The RNA polymerase II C‐terminal heptad repeat domain (CTD) is essential for normal transcription and co‐transcriptional processing of mRNA precursors. The mammalian CTD comprises 52 heptads whose consensus, YSPTSPS, is conserved throughout eukaryotes, followed by a 10 amino acid C‐terminal sequence that is conserved only among vertebrates. Here we show that surprisingly, the heptad repeats are not sufficient to support efficient transcription, pre‐mRNA processing or full cell viability. In addition to the heptads, the 10 amino acid C‐terminal motif is essential for high level transcription, splicing and poly(A) site cleavage. Efficient mRNA synthesis from a transiently transfected reporter gene required the C‐terminal motif plus between 16 and 25 heptad repeats from either the N‐ or C‐terminal half of the CTD. Twenty‐seven consensus heptads plus the C‐terminal motif also supported efficient mRNA synthesis but not cell viability.