Evidence map›Paper›PMID 25887984›Full record

ArticleBMC evolutionary biology2015

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

Corinne N Simonti, Katherine S Pollard, Sebastian Schröder, Daniel He, Benoit G Bruneau, Melanie Ott, John A Capra

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 21 citations in OpenAlex.

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  11. The pol II CTD: new twists in the tail.Nature structural & molecular biology · 2016
    Review
  12. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Corinne N SimontiCenter for Human Genetics Research, Vanderbilt University, Nashville, TN, 37232, USA. corinne.n.simonti@vanderbilt.edu.
Katherine S PollardGladstone Institutes, University of California, San Francisco, San Francisco, CA, 94158, USA. katherine.pollard@gladstone.ucsf.edu.
Sebastian SchröderGladstone Institutes, University of California, San Francisco, San Francisco, CA, 94158, USA. caredgo@gmail.com.
Daniel HeGladstone Institutes, University of California, San Francisco, San Francisco, CA, 94158, USA. daniel.he@gladstone.ucsf.edu.
Benoit G BruneauGladstone Institutes, University of California, San Francisco, San Francisco, CA, 94158, USA. bbruneau@gladstone.ucsf.edu.
Melanie OttGladstone Institutes, University of California, San Francisco, San Francisco, CA, 94158, USA. mott@gladstone.ucsf.edu.
John A CapraCenter for Human Genetics Research, Vanderbilt University, Nashville, TN, 37232, USA. tony.capra@vanderbilt.edu.
University of California, San Francisco · USCenter for Human Genetics · USVanderbilt University · US

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
Role of Factor Acetylation in the Regulation of HIV TranscriptionR01AI083139 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI OTT, MELANIE MARIA · 2009 to 2017
$3.9M
What Made Us Human?R01GM082901 · NIGMS · J. DAVID GLADSTONE INSTITUTES · PI POLLARD, KATHERINE S. · 2008 to 2011
$1.4M
Training Program in Quantitative Ocular GenomicsT32EY021453 · NEI · VANDERBILT UNIVERSITY · PI BRANTLEY, MILAM A, COX, NANCY J · 2011 to 2020
$1.4M
NEI NIH HHS 5T32EY021453NEI NIH HHS T32 EY021453NIAID NIH HHS P30 AI027763NIAID NIH HHS R01 AI083139NIAID NIH HHS R01AI083139NIGMS NIH HHS R01 GM082901NIGMS NIH HHS R01GM082901
6 · The paper itself

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.

Indexed as

Evolution, MolecularAcetylationAnimalsCell AdhesionCell Growth ProcessesGene Expression RegulationHumansLysineMammalsPromoter Regions, GeneticProtein Structure, TertiaryRNA Polymerase IIVertebratesLysineRNA Polymerase II

Identifiers

PMID25887984
PMCPMC4362643
OpenAlexW1988404005

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.