Evolution of the RNA polymerase II C-terminal domain

Abstract

In recent years a great deal of biochemical and genetic research has focused on the C-terminal domain (CTD) of the largest subunit (RPB1) of DNA-dependent RNA polymerase II. This strongly conserved domain of tandemly repeated heptapeptides has been linked functionally to important steps in the initiation and processing of mRNA transcripts in both animals and fungi. Although they are absolutely required for viability in these organisms, C-terminal tandem repeats do not occur in RPB1 sequences from diverse eukaryotic taxa. Here we present phylogenetic analyses of RPB1 sequences showing that canonical CTD heptads are strongly conserved in only a subset of eukaryotic groups, all apparently descended from a single common ancestor. Moreover, eukaryotic groups in which the most complex patterns of ontogenetic development occur are descended from this CTD-containing ancestor. Consistent with the results of genetic and biochemical investigations of CTD function, these analyses suggest that the enhanced control over RNA polymerase II transcription conveyed by acquired CTD͞protein interactions was an important step in the evolution of intricate patterns of gene expression that are a hallmark of large, developmentally complex eukaryotic organisms. development ͉ RPB1 ͉ transcription E ach of the core subunits present in all cellular DNAdependent RNA polymerase (pol) enzymes shares a common evolutionary origin (1, 2). The largest of these subunits contains eight highly conserved domains, designated regions A through H (2), which are common to all prokaryotic and eukaryotic homologues (3). Unlike all other members of this protein family, however, the largest subunit of eukaryotic RNA pol II has an additional C-terminal domain (CTD), comprising a varied number of tandemly repeated heptapeptides with the consensus sequence Tyr-1-Ser-2-Pro-3-Thr-4 -Ser-5-Pro-6 -Ser-7 (4). In animals and yeast, where the mechanics of transcription are understood most clearly, the CTD has become a focal point of investigations into the interactions between RNA pol II and a variety of transcription-related proteins.Reversible phosphorylation of the CTD regulates the cycling of RNA pol II between a hypophosphorylated (IIO) form, which is competent to enter the preinitiation complex, and a hyperphosphorylated (IIA) form capable of processive transcript elongation (5). Throughout this cycle the CTD binds essential transcription-related proteins that help to regulate gene expression (6-9), promote efficient elongation (10), and effectively couple transcription to pre-mRNA processing (11-15). So central is its role in these interactions that the CTD has been called, by one reviewer, ''the tail that wags the dog'' of RNA pol II (16).Tandemly repeated CTD heptads occur in all RNA pol II largest subunits isolated to date from animals, fungi, and green plants. Given the importance of the CTD for pol II function, it is not surprising that it has been conserved so strongly during the evolution of these groups. A typical CTD also is present in certain protists;...

Phylogeny of Opisthokonta and the evolution of multicellularity and complexity in Fungi and Metazoa

“…Certainly, multicellularity is homoplastic among many clades, perhaps as many as 24 (Buss 1987). However, the major multicellular kingdoms belong to a clade that includes Opisthokonta and Chlorobiota, and innovations in molecular mechanisms may have permitted the rise of true multicellularity in complex body plans (see Stiller & Hall 2002). Reductions in size and complexity within multicellular clades are also well known.…”

The Soh1/MED31 Protein Is an Ancient Component of Schizosaccharomyces pombe and Saccharomyces cerevisiae Mediator

“…The Mediator complex interacts directly with CTD (23,31), and the nine SRB genes encoding for Mediator subunits were first identified in a screen for mutants, which suppress the cold-sensitive phenotype of a CTD truncation mutant (34). We were therefore surprised to find conserved Soh1/MED31 orthologues in protists like G. intestinalis and P. falciparum, which lack the canonical CTD repeat structure (33). The observation suggests that an ancient Mediator-like factor might be involved in passing signals from activators and repressors to the RNAP II in eukaryotes that diverged before the establishment of the canonical heptapeptide repeats CTD structure.…”

“…The CTD of RNAP II plays a central part in the entire process of transcription, including initiation, capping of the primary transcript, splicing, and 3Ј processing. Phylogenetic analyses of Rpb1 sequences have led to the suggestion that canonical CTD heptads (YSPTSPS) are strongly conserved in only a subset of eukaryotic groups, including fungi, animals, plants, and some protists, which display complex patterns of ontogenetic development (33). According to this theory, the enhanced control over RNAP II transcription conveyed by ac- quired CTD-protein interactions was an important step in the evolution of intricate patterns of gene expression that are a hallmark of large, developmentally complex eukaryotic organisms (33).…”

Foraminifera and Cercozoa share a common origin according to RNA polymerase II phylogenies

“…In our ML analysis, opisthokonts do not form a monophyletic group and the clade consisting of fungi and microsporidia branches somewhat deeply, although this was not the case in distance trees (data not shown). In a recent RPB1 phylogeny, an opisthokont clade was observed but its support varied greatly (Stiller & Hall, 2002;Dacks et al, 2002).…”