RNA editing: a driving force for adaptive evolution?

Gommans, Willemijn M.; Mullen, Sean P.; Maas, Stefan

doi:10.1002/bies.200900045

Cited by 130 publications

(149 citation statements)

References 80 publications

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“…Among all 5965 A-to-G sites in U87MG cells, 31% have editing levels no more than 0.2, whereas only 5% have values greater than or equal to 0.8. The enrichment of low-level editing is consistent with the continuous probing (COP) hypothesis proposed by Maas and colleagues (Gommans et al 2009). According to this hypothesis, low-level editing is prevalent due to COP of the transient and dynamic RNA secondary structures by the editing machinery.…”

Section: Discussionsupporting

confidence: 89%

Accurate identification of A-to-I RNA editing in human by transcriptome sequencing

Bahn¹,

Lee²,

Li³

et al. 2011

Genome Res.

315

355

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RNA editing enhances the diversity of gene products at the post-transcriptional level. Approaches for genome-wide identification of RNA editing face two main challenges: separating true editing sites from false discoveries and accurate estimation of editing levels. We developed an approach to analyze transcriptome sequencing data (RNA-seq) for global identification of RNA editing in cells for which whole-genome sequencing data are available. We applied the method to analyze RNA-seq data of a human glioblastoma cell line, U87MG. Around 10,000 DNA-RNA differences were identified, the majority being putative A-to-I editing sites. These predicted A-to-I events were associated with a low false-discovery rate (~5%). Moreover, the estimated editing levels from RNA-seq correlated well with those based on traditional clonal sequencing. Our results further facilitated unbiased characterization of the sequence and evolutionary features flanking predicted A-to-I editing sites and discovery of a conserved RNA structural motif that may be functionally relevant to editing. Genes with predicted A-to-I editing were significantly enriched with those known to be involved in cancer, supporting the potential importance of cancer-specific RNA editing. A similar profile of DNA-RNA differences as in U87MG was predicted for another RNA-seq data set obtained from primary breast cancer samples. Remarkably, significant overlap exists between the putative editing sites of the two transcriptomes despite their difference in cell type, cancer type, and genomic backgrounds. Our approach enabled de novo identification of the RNA editome, which sets the stage for further mechanistic studies of this important step of post-transcriptional regulation.

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Section: Discussionsupporting

confidence: 89%

Accurate identification of A-to-I RNA editing in human by transcriptome sequencing

Bahn¹,

Lee²,

Li³

et al. 2011

Genome Res.

315

355

View full text Add to dashboard Cite

show abstract

“…Thus, low level editing sites might contribute to efficient adaptive evolution without changing the genome. 80 However, proteins with low editing levels have not been studied so far. Further studies will show whether low editing levels are due to low binding or reduced activity of ADAR.…”

Section: Regulation Of Adar Activitymentioning

confidence: 99%

Proteome diversification by adenosine to inosine RNA-editing

Pullirsch

Jantsch²

2010

RNA Biology

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“…RNA editing is the umbrella term for several mechanisms that generate nucleotide insertions or deletions as well as base conversions in RNA (Simpson and Emeson 1996). An evolutionary advantage of RNA editing in comparison to DNA level changes is flexibility regarding spatial and temporal regulation, as well as a capacity for quick adaptation to environmental changes (Gommans et al 2009;Nishikura 2010). The most widespread type of RNA editing in higher eukaryotes is known as adenosine-to-inosine (A-to-I) RNA editing.…”

Section: Introductionmentioning

confidence: 99%

Evolutionary and ontogenetic changes in RNA editing in human, chimpanzee, and macaque brains

Bammann

et al. 2013

RNA

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Adenosine-to-inosine (A-to-I) substitutions are the most common type of RNA editing in mammals. A-to-I RNA editing is particularly widespread in the brain and is known to play important roles in neuronal functions. In this study we investigated RNA-editing changes during human brain development and maturation, as well as evolutionary conservation of RNA-editing patterns across primates. We used high-throughput transcriptome sequencing (RNA-seq) to quantify the RNA-editing levels and assess ontogenetic dynamics of RNA editing at more than 8000 previously annotated exonic A-to-I RNA-editing sites in two brain regions-prefrontal cortex and cerebellum-of humans, chimpanzees, and rhesus macaques. We observed substantial conservation of RNA-editing levels between the brain regions, as well as among the three primate species. Evolutionary changes in RNA editing were nonetheless evident, with 40% of the annotated editing sites studied showing divergent editing levels among the three species and 16.5% of sites displaying statistically significant human-specific editing patterns. Across lifespan, we observed an increase of the RNA-editing level with advanced age in both brain regions of all three primate species.

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RNA editing: a driving force for adaptive evolution?

Cited by 130 publications

References 80 publications

Accurate identification of A-to-I RNA editing in human by transcriptome sequencing

Accurate identification of A-to-I RNA editing in human by transcriptome sequencing

Proteome diversification by adenosine to inosine RNA-editing

Evolutionary and ontogenetic changes in RNA editing in human, chimpanzee, and macaque brains

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