The 5' guanine-N7 cap is the first cotranscriptional modification of messenger
RNA. In Saccharomyces cerevisiae, the first two steps in capping are catalyzed
by the RNA triphosphatase Cet1 and RNA guanylyltransferase Ceg1, which form a
complex that is directly recruited to phosphorylated RNA polymerase II (RNAP
IIo), primarily via contacts between RNAP IIo and Ceg1. A 3.0 A crystal
structure of Cet1-Ceg1 revealed a 176 kDa heterotetrameric complex composed of
one Cet1 homodimer that associates with two Ceg1 molecules via interactions
between the Ceg1 oligonucleotide binding domain and an extended Cet1 WAQKW amino
acid motif. The WAQKW motif is followed by a flexible linker that would allow
Ceg1 to achieve conformational changes required for capping while maintaining
interactions with both Cet1 and RNAP IIo. The impact of mutations as assessed
through genetic analysis in S. cerevisiae is consonant with contacts observed in
the Cet1-Ceg1 structure.
