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EMBO J. 2003 Aug 15;22(16):4274-82.

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

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Department of Biochemistry and Molecular Genetics, UCHSC, B121, 4200 E. 9th Avenue, Denver, CO 80262, USA.


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.

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