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Evolution of lysine acetylation in the RNA polymerase II C-terminal domain.

Simonti CN, Pollard KS, Schröder S, He D, Bruneau BG, Ott M, Capra JA - BMC Evol. Biol. (2015)

Bottom Line: Genes occupied and regulated by acRPB1 show significant enrichment for evolutionary origins in the early history of eukaryotes through early vertebrates.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Human Genetics Research, Vanderbilt University, Nashville, TN, 37232, USA. corinne.n.simonti@vanderbilt.edu.

ABSTRACT

Background: RPB1, 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.

Results: To 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.

Conclusions: Our 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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The human RNA polymerase II subunit 1 (RPB1) C-terminal domain (CTD) contains more heptad repeats than the yeasts, and eight of its non-consensus distal repeats have a lysine residue. In this schematic of the RPB1 CTD for two species of yeast and human, consensus heptad repeats (YSPTSPS) are colored dark gray; repeats with a lysine at position 7 are colored red; and all other non-consensus repeats are in white.
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Fig1: The human RNA polymerase II subunit 1 (RPB1) C-terminal domain (CTD) contains more heptad repeats than the yeasts, and eight of its non-consensus distal repeats have a lysine residue. In this schematic of the RPB1 CTD for two species of yeast and human, consensus heptad repeats (YSPTSPS) are colored dark gray; repeats with a lysine at position 7 are colored red; and all other non-consensus repeats are in white.

Mentions: The RPB1 CTD has undergone considerable change during the evolution of eukaryotes [16]. While the consensus repeat sequence Y1S2P3T4S5P6S7 is conserved from yeast to mammals, the number of repeats varies: S. cerevisiae has only 26 repeats, while humans have 52 (Figure 1). Conserved heptad repeats are found in the linker-proximal part of the mammalian CTD, but the sequence of the distal heptad repeats, which are not present in yeast, diverge from this consensus sequence. Eight of the non-consensus repeats in human and mouse CTDs carry a lysine at position 7 (K7), rather than serine.Figure 1


Evolution of lysine acetylation in the RNA polymerase II C-terminal domain.

Simonti CN, Pollard KS, Schröder S, He D, Bruneau BG, Ott M, Capra JA - BMC Evol. Biol. (2015)

The human RNA polymerase II subunit 1 (RPB1) C-terminal domain (CTD) contains more heptad repeats than the yeasts, and eight of its non-consensus distal repeats have a lysine residue. In this schematic of the RPB1 CTD for two species of yeast and human, consensus heptad repeats (YSPTSPS) are colored dark gray; repeats with a lysine at position 7 are colored red; and all other non-consensus repeats are in white.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4362643&req=5

Fig1: The human RNA polymerase II subunit 1 (RPB1) C-terminal domain (CTD) contains more heptad repeats than the yeasts, and eight of its non-consensus distal repeats have a lysine residue. In this schematic of the RPB1 CTD for two species of yeast and human, consensus heptad repeats (YSPTSPS) are colored dark gray; repeats with a lysine at position 7 are colored red; and all other non-consensus repeats are in white.
Mentions: The RPB1 CTD has undergone considerable change during the evolution of eukaryotes [16]. While the consensus repeat sequence Y1S2P3T4S5P6S7 is conserved from yeast to mammals, the number of repeats varies: S. cerevisiae has only 26 repeats, while humans have 52 (Figure 1). Conserved heptad repeats are found in the linker-proximal part of the mammalian CTD, but the sequence of the distal heptad repeats, which are not present in yeast, diverge from this consensus sequence. Eight of the non-consensus repeats in human and mouse CTDs carry a lysine at position 7 (K7), rather than serine.Figure 1

Bottom Line: Genes occupied and regulated by acRPB1 show significant enrichment for evolutionary origins in the early history of eukaryotes through early vertebrates.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Human Genetics Research, Vanderbilt University, Nashville, TN, 37232, USA. corinne.n.simonti@vanderbilt.edu.

ABSTRACT

Background: RPB1, 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.

Results: To 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.

Conclusions: Our 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.

Show MeSH
Related in: MedlinePlus