RNA polymerase II transcriptional fidelity control and its functional interplay with DNA modifications

Xu, Liang; Wang, Wei; Chong, Jenny; Shin, Ji Hyun; Xu, Jun; Wang, Dong

doi:10.3109/10409238.2015.1087960

Cited by 25 publications

(30 citation statements)

References 205 publications

(341 reference statements)

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“…17–19 During transcription elongation, RNA pol II travels along the DNA template strand and may encounter all kinds of transcriptional obstructions, including covalent DNA lesions and epigenetic DNA modifications. 17–19 These DNA modifications can affect the template recognition by RNA pol II and lead to distinct transcriptional outcomes (transcriptional pausing/stalling, lesion bypass, arrest) and downstream biological processes.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic DNA Modification N⁶-Methyladenine Causes Site-Specific RNA Polymerase II Transcriptional Pausing

Wang¹,

et al. 2017

J. Am. Chem. Soc.

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N 6-Methyladenine (N6-mA or 6 mA) is an epigenetic DNA modification in eukaryotic genomes. In contrast to the well-established roles of 5-methylcytosine for epigenetic regulation of gene expression, the functional roles of N6-mA remain elusive. In particular, the impact of N6-mA modification of the DNA template on RNA polymerase II (pol II) transcription elongation is not known. In this work, using the Saccharomyces cerevisiae pol II transcriptional elongation system as a model, we investigated the molecular mechanism of pol II recognition and processing of N6-mA sites via both biochemical and structural approaches. We found that N6-mA causes site-specific pol II pausing/stalling. Structural analysis revealed that while N6-mA can reach the +1 template position, the stability of the N6-mA and UTP base pairing is compromised. Taken together, we reveal that the presence of the 6-methyl group on adenine reduces incorporation efficiency and promotes backtracking translocation. Our studies with yeast pol II provide molecular insights into understanding the impacts of N6-mA on pol II transcription dynamics in different organisms.

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Section: Introductionmentioning

confidence: 99%

Epigenetic DNA Modification N⁶-Methyladenine Causes Site-Specific RNA Polymerase II Transcriptional Pausing

Wang¹,

et al. 2017

J. Am. Chem. Soc.

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“…the anti-sense strand) may slow the rate of transcription elongation, much like the premise for SMRT sequencing described for DNA polymerase. This has been described for various DNA modifications including m6A in eukaryotic systems (45, 46), however the effects of m6A modification on prokaryote RNA polymerase kinetics is not known. Nonetheless, it is possible that overrepresentation of m6A modifications on the sense strand of genes may minimize any potential effects on RNA polymerase kinetics in B. burgdorferi .…”

Section: Resultsmentioning

confidence: 97%

DNA Methylation by Restriction Modification Systems Affects the Global Transcriptome Profile inBorrelia burgdorferi

Casselli

Tourand

Scheidegger

et al. 2018

Preprint

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22Prokaryote restriction modification (RM) systems serve to protect bacteria from potentially 23 detrimental foreign DNA. Recent evidence suggests that DNA methylation by the 24 methyltransferase (MTase) components of RM systems can also have effects on transcriptome 25 profiles. The causative agent of Lyme disease, Borrelia burgdorferi, encodes two RM systems 26 with N6-Methyladenosine (m6A) MTase activity. The specific recognition and/or methylation 27 sequences have not been identified for either B. burgdorferi MTase, and it is not currently known 28 whether these RM systems influence transcriptome profiles. In the current study, Single Molecule 29Real Time sequencing was utilized to map genome-wide m6A sites, and to identify consensus 30 modified motifs in wild-type B. burgdorferi as well as isogenic MTase mutants. Four conserved 31 m6A motifs were identified, and were fully attributable to the presence of specific MTases. Whole-32 genome transcriptome changes were observed in conjunction with the loss of MTase enzymes, 33 indicating that DNA methylation by RM systems has effects on gene expression in B. burgdorferi. 34

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“…For example, chemical modifications in transcribed DNA can lead to the biogenesis of new RNAs and proteins, which could contribute to cell survival. As a consequence, only cells bearing the DNA chemical modifications can divide, and therefore having the DNA chemical modifications would increase the probability of giving rise to genetically adapted daughter cells [157][158][159][160][161][162] (Figure 4D). The same principle can be used to establish a direct link between genetic adaptation and epigenetic modifications (i.e., DNA or histone chemical modifications that impact gene expression), as environmental fluctuations induce epigenetic modifications of specific loci as part of the cells' physiological adaptation.…”

Section: Physiological Adaptation Facilitates Genetic Adaptation: Rolmentioning

confidence: 99%

Physicochemical Foundations of Life that Direct Evolution: Chance and Natural Selection are not Evolutionary Driving Forces

Auboeuf

2020

Life

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The current framework of evolutionary theory postulates that evolution relies on random mutations generating a diversity of phenotypes on which natural selection acts. This framework was established using a top-down approach as it originated from Darwinism, which is based on observations made of complex multicellular organisms and, then, modified to fit a DNA-centric view. In this article, it is argued that based on a bottom-up approach starting from the physicochemical properties of nucleic and amino acid polymers, we should reject the facts that (i) natural selection plays a dominant role in evolution and (ii) the probability of mutations is independent of the generated phenotype. It is shown that the adaptation of a phenotype to an environment does not correspond to organism fitness, but rather corresponds to maintaining the genome stability and integrity. In a stable environment, the phenotype maintains the stability of its originating genome and both (genome and phenotype) are reproduced identically. In an unstable environment (i.e., corresponding to variations in physicochemical parameters above a physiological range), the phenotype no longer maintains the stability of its originating genome, but instead influences its variations. Indeed, environment- and cellular-dependent physicochemical parameters define the probability of mutations in terms of frequency, nature, and location in a genome. Evolution is non-deterministic because it relies on probabilistic physicochemical rules, and evolution is driven by a bidirectional interplay between genome and phenotype in which the phenotype ensures the stability of its originating genome in a cellular and environmental physicochemical parameter-depending manner.

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RNA polymerase II transcriptional fidelity control and its functional interplay with DNA modifications

Cited by 25 publications

References 205 publications

Epigenetic DNA Modification N⁶-Methyladenine Causes Site-Specific RNA Polymerase II Transcriptional Pausing

Epigenetic DNA Modification N⁶-Methyladenine Causes Site-Specific RNA Polymerase II Transcriptional Pausing

DNA Methylation by Restriction Modification Systems Affects the Global Transcriptome Profile inBorrelia burgdorferi

Physicochemical Foundations of Life that Direct Evolution: Chance and Natural Selection are not Evolutionary Driving Forces

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RNA polymerase II transcriptional fidelity control and its functional interplay with DNA modifications

Cited by 25 publications

References 205 publications

Epigenetic DNA Modification N6-Methyladenine Causes Site-Specific RNA Polymerase II Transcriptional Pausing

Epigenetic DNA Modification N6-Methyladenine Causes Site-Specific RNA Polymerase II Transcriptional Pausing

DNA Methylation by Restriction Modification Systems Affects the Global Transcriptome Profile inBorrelia burgdorferi

Physicochemical Foundations of Life that Direct Evolution: Chance and Natural Selection are not Evolutionary Driving Forces

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Epigenetic DNA Modification N⁶-Methyladenine Causes Site-Specific RNA Polymerase II Transcriptional Pausing

Epigenetic DNA Modification N⁶-Methyladenine Causes Site-Specific RNA Polymerase II Transcriptional Pausing