ArticleBMC evolutionary biology2015
Evolution of lysine acetylation in the RNA polymerase II C-terminal domain.
Article in BMC evolutionary biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 21 citations in OpenAlex.
- Kaposi's Sarcoma-associated herpesvirus uses a novel protein fold to hijack RNA Polymerase II for viral late gene transcription.bioRxiv : the preprint server for biology · 2026Article
- Transcription activation depends on the length of the RNA polymerase II C-terminal domain.The EMBO journal · 2021Article
- Contractions of the C-Terminal Domain ofG3 (Bethesda, Md.) · 2020Article
- A combinatorial view of old and new RNA polymerase II modifications.Transcription · 2020Review
- Crosstalk between RNA Pol II C-Terminal Domain Acetylation and Phosphorylation via RPRD Proteins.Molecular cell · 2019Article
- The C-Terminal Domain of RNA Polymerase II Is a Multivalent Targeting Sequence that Supports Drosophila Development with Only Consensus Heptads.Molecular cell · 2019Article
- RNA polymerase II clustering through carboxy-terminal domain phase separation.Nature structural & molecular biology · 2018Article
- Discerning evolutionary trends in post-translational modification and the effect of intrinsic disorder: Analysis of methylation, acetylation and ubiquitination sites in human proteins.PLoS computational biology · 2018Article
- Lysine Acetylation Goes Global: From Epigenetics to Metabolism and Therapeutics.Chemical reviews · 2018Review
- Phosphorylation induces sequence-specific conformational switches in the RNA polymerase II C-terminal domain.Nature communications · 2017Article
- The pol II CTD: new twists in the tail.Nature structural & molecular biology · 2016Review
- DNA Instability Maintains the Repeat Length of the Yeast RNA Polymerase II C-terminal Domain.The Journal of biological chemistry · 2016Article
- Methylation of RNA polymerase II non-consensus Lysine residues marks early transcription in mammalian cells.eLife · 2015Article
- Site-specific methylation and acetylation of lysine residues in the C-terminal domain (CTD) of RNA polymerase II.Transcription · 2015Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundRPB1, the largest subunit of RNA polymerase II, contains a highly modifiable C-terminal domain (CTD) that consists of variations of a consensus heptad repeat sequence (Y1S2P3T4S5P6S7). The consensus CTD repeat motif and tandem organization represent the ancestral state of eukaryotic RPB1, but across eukaryotes CTDs show considerable diversity in repeat organization and sequence content. These differences may reflect lineage-specific CTD functions mediated by protein interactions. Mammalian CTDs contain eight non-consensus repeats with a lysine in the seventh position (K7). Posttranslational acetylation of these sites was recently shown to be required for proper polymerase pausing and regulation of two growth factor-regulated genes.
resultsTo investigate the origins and function of RPB1 CTD acetylation (acRPB1), we computationally reconstructed the evolution of the CTD repeat sequence across eukaryotes and analyzed the evolution and function of genes dysregulated when acRPB1 is disrupted. Modeling the evolutionary dynamics of CTD repeat count and sequence content across diverse eukaryotes revealed an expansion of the CTD in the ancestors of Metazoa. The new CTD repeats introduced the potential for acRPB1 due to the appearance of distal repeats with lysine at position seven. This was followed by a further increase in the number of lysine-containing repeats in developmentally complex clades like Deuterostomia. Mouse genes enriched for acRPB1 occupancy at their promoters and genes with significant expression changes when acRPB1 is disrupted are enriched for several functions, such as growth factor response, gene regulation, cellular adhesion, and vascular development. Genes occupied and regulated by acRPB1 show significant enrichment for evolutionary origins in the early history of eukaryotes through early vertebrates.
conclusionsOur combined functional and evolutionary analyses show that RPB1 CTD acetylation was possible in the early history of animals, and that the K7 content of the CTD expanded in specific developmentally complex metazoan lineages. The functional analysis of genes regulated by acRPB1 highlight functions involved in the origin of and diversification of complex Metazoa. This suggests that acRPB1 may have played a role in the success of animals.
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