Two major forms of RNA Pol II exist in eukaiyotic cells: the hypophosphorylated Pol Ha or the hyperphosphorylated RNA Pol Ho. In Pol Ho, the carboxy-terminal domain (CTD) of the largest subunit (Rpbl) of Pol II is extensively phosphorylated (Lin et al, 2002; Svejstrup, 2004). The CTD consists of heptapeptide repeats with a consensus sequence YIS2P3T4S5P6S7, which is conserved throughout the eukaryotic kingdom. However, the number of the repeats varies among different species. The CTD of S. cerevisiae Pol II has 26 repeats, while C. elegans has 32, Drosophila 42, and mammals contain 52 repeats (Allison et al, 1985; Corden et al., 1985; Dahmus, 1995; Kobor and Greenblatt, 2002; Oelgeschlager, 2002). For a given species, there is a set threshold number of heptapeptide repeats that is critical for Pol II to exert its full function. For example, a minimal length of 9 repeats in yeast or 28 repeats in human cells is necessary for cell survival. Yeast strains with a mutant Pol II containing between 9 and 20 repeats are cold-sensitive and display defects in the transcription of a number of genes (Allison et al., 1988; Nonet et al., 1987). On the other hand, mice with a Pol II that has only 39 repeats are either growth retarded or display an increased neonatal lethality (Litingtung et al., 1999). The reason for the requirement for a critical number of heptapeptide repeats within the CTD is because during transcription the CTD interacts with a variety of accessory factors functioning at different stages of the transcription cycle and also serves as a platform for the operation of various machineries involved in co-transcriptional processing. This point is illustrated by the observations that the truncation of the CTD causes defects not only in transcription but also in pre-mRNA capping, splicing as well as cleavage/polyadenylation (Kobor and Greenblatt, 2002; McCracken et al., 1997; McCracken et al., 1997; West and Corden, 1995).

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