Fig 1.
The role of the RNA polymerase II CTD in recruiting different factors to the transcription complex.
(A) Transcription of a typical mRNA. Top: a representation of a housekeeping gene with three exons (gray boxes) and two introns. Recruitment of an mRNA producing RNA pol II complex to the promoter results in the production of a transcript that is capped, spliced, polyadenylated, and exported from the nucleus for translation. Bottom: a representation of the DNA strand wrapped around histones (blue ovals). The RNA pol II complex is shown in green, with the CTD shown as an extension. In eukaryotes, the CTD consists of a series of repeats of the amino acid sequence YSPTSPS/K. The serines in the second and fifth positions of each repeat are shown as blue circles labeled 2 and 5, respectively. Three repeats are shown, although the number can vary according to species (n). In P. falciparum, 12–17 repeats have been reported. Phosphorylation of the serines are shown as orange circles labeled with a P and are found primarily on serines in the fifth position near the beginning of transcription, on the serines in both positions at the middle of the transcription unit, and at the serines in the second position where transcription terminates. The alternate phosphorylated states mediate recruitment of different factors required for mRNA production and maturation, as well as histone modifiers, including SET1 (red oval), which deposits the epigenetic mark H3K4me3 concurrent with the production of an mRNA. Thus, this mark is found at transcriptionally active regions of the genome. (B) A model for transcription of a noncoding RNA (ncRNA) at var loci. Top: a promoter found within the introns of var genes leads to the production of ncRNAs that are capped but not polyadenylated. In addition, they are retained within the nucleus and associated with chromatin. Middle: the RNA pol II complex is engaged in transcribing a noncoding RNA; however, the modifications of the serines at positions 2 and 5 of the CTD and the transcription-related factors that are recruited to the complex are unknown (?). PfSET2 (purple oval) has been shown to bind directly to the CTD and to deposit the epigenetic mark H3K36me3 at both active and silent var genes. This is consistent with its recruitment by RNA pol II when it is transcribing the ncRNA from the promoter located within var introns. Bottom: a dominant-negative version of PfSET2 (dark green ovals) that is not capable of depositing the H3K36me3 mark can compete with the endogenous wild-type PfSET2 for binding to the CTD. Overexpression of the dominant-negative protein reduces the efficiency of PfSET2 recruitment to var loci and leads to switching to var2csa.