Comparative analysis of A-to-I editing in human and non-human primate brains reveals conserved patterns and context-dependent regulation of RNA editing

O’Neil, Richard T.; Wang, Xiaojing; Morabito, Michael V.; Emeson, Ronald B.

doi:10.1186/s13041-017-0291-1

Cited by 10 publications

(20 citation statements)

References 24 publications

(27 reference statements)

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“…Also, it has been shown that GABRA3 is targeted by both ADARs enzymes (Ohlson et al, 2007). Interestingly, the editing site on GABRA3 was already reported in different animals such as human (Nicholas et al, 2010, O'Neil et al, 2017, mouse (Daniel et al, 2011), pig (Venø et al, 2012), bovine (Bakhtiarizadeh et al, 2018), rat, rabbit, dog, frog (Daniel et al, 2011) and chicken embryos (Daniel et al, 2011, Frésard et al, 2015. This result suggests that editing events may contribute to amino acid functional conservation throughout the evolution of vertebrates, as has been reported in previous study in chicken (Roux et al, 2016).…”

Section: )supporting

confidence: 76%

Large-scale RNA editing profiling in different adult chicken tissues

Shafiei

Salehi

2018

Preprint

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RNA editing is a post-transcription maturation process that diversifies genomically encoded information and can lead to diversity and complexity of transcriptome, especially in the brain.Thanks to next-generation sequencing technologies, a large number of editing sites have been identified in different species, especially in human, mouse and rat. While this mechanism is well described in mammals, only a few studies have been performed in the chicken. Here, we developed a rigorous computational strategy to identify RNA editing sites in eight different tissues of the chicken (brain, spleen, colon, lung, kidney, heart, testes and liver), based on RNA sequencing data alone. We identified 68 A-to-G editing sites in 46 genes. Only two of these were previously reported in chicken. We found no C-to-U sites, attesting the lack of this type of editing mechanism in the chicken. Similar to mammals, the editing sites were enriched in non-coding regions, rarely resulted in change of amino acids, showed a critical role in nervous system and had a low guanosine level upstream of the editing site and some enrichment downstream from the site.Moreover, in contrast to mammals, editing sites were weakly enriched in interspersed repeats and the frequency and editing ratio of non-synonymous sites were higher than those of synonymous sites.Interestingly, we found several tissue-specific edited genes including GABRA3, SORL1 and HTR1D in brain and RYR2 and FHOD3 in heart that were associated with functional processes relevant to the corresponding tissue. This finding highlighted the importance of the RNA editing in several chicken tissues, especially the brain. This study extends our understanding of RNA editing in chicken tissues and establish a foundation for further exploration of this process.

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Section: )supporting

confidence: 76%

Large-scale RNA editing profiling in different adult chicken tissues

Shafiei

Salehi

2018

Preprint

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“…We used the mmPCR-seq method to detect A-to-I editing at 146 pre-selected sites in two regions in the rat brain. While changes in A-to-I RNA editing in the rat were previously demonstrated in cortical cultures and brain samples [ 50 , 51 , 53 , 54 ], this is the first use of mmPCR-seq to quantify editing changes in rat brain tissue at multiple sites. For some sites (e.g., Celf4 , Ankrd28 ), editing is demonstrated for the first time in the rat; editing levels at these sites is largely conserved with the corresponding human and mouse orthologs.…”

Section: Discussionmentioning

confidence: 86%

“…2 and Fig. 4 , raising the concern that PFC samples were contaminated during extraction with choroid plexus (CP) tissue (where Htr2c expression is high but A and B site editing levels are low) [ 51 ]. We thus assessed the expression of the CP marker Coagulation factor V F5 [ 52 ] in O1-C ( n = 5) and O1-PRS ( n = 6) samples with both low and high A and B site editing.…”

Section: Resultsmentioning

confidence: 99%

A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations

et al. 2018

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BackgroundAdenosine-to-inosine (A-to-I) RNA editing is an epigenetic modification catalyzed by adenosine deaminases acting on RNA (ADARs), and is especially prevalent in the brain. We used the highly accurate microfluidics-based multiplex PCR sequencing (mmPCR-seq) technique to assess the effects of development and environmental stress on A-to-I editing at 146 pre-selected, conserved sites in the rat prefrontal cortex and amygdala. Furthermore, we asked whether changes in editing can be observed in offspring of stress-exposed rats. In parallel, we assessed changes in ADARs expression levels.ResultsIn agreement with previous studies, we found editing to be generally higher in adult compared to neonatal rat brain. At birth, editing was generally lower in prefrontal cortex than in amygdala. Stress affected editing at the serotonin receptor 2c (Htr2c), and editing at this site was significantly altered in offspring of rats exposed to prereproductive stress across two generations. Stress-induced changes in Htr2c editing measured with mmPCR-seq were comparable to changes measured with Sanger and Illumina sequencing. Developmental and stress-induced changes in Adar and Adarb1 mRNA expression were observed but did not correlate with editing changes.ConclusionsOur findings indicate that mmPCR-seq can accurately detect A-to-I RNA editing in rat brain samples, and confirm previous accounts of a developmental increase in RNA editing rates. Our findings also point to stress in adolescence as an environmental factor that alters RNA editing patterns several generations forward, joining a growing body of literature describing the transgenerational effects of stress.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4409-8) contains supplementary material, which is available to authorized users.

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“…The calcium‐dependent secretion activator 1 (CADPS) is shown to participate in calcium‐dependent release of synaptic vesicles . This was the only protein from our list whose ortholog was also edited in the fruit fly proteome .…”

Section: Resultsmentioning

confidence: 99%

Adenosine‐to‐Inosine RNA Editing in Mouse and Human Brain Proteomes

et al. 2019

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Proteogenomics is based on the use of customized genome or RNA sequencing databases for interrogation of shotgun proteomics data in search for proteome‐level evidence of genome variations or RNA editing. In this work, the products of adenosine‐to‐inosine RNA editing in human and murine brain proteomes are identified using publicly available brain proteome LC‐MS/MS datasets and an RNA editome database compiled from several sources. After filtering of false‐positive results, 20 and 37 sites of editing in proteins belonging to 14 and 32 genes are identified for murine and human brain proteomes, respectively. Eight sites of editing identified with high spectral counts overlapped between human and mouse brain samples. Some of these sites have been previously reported using orthogonal methods, such as α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) glutamate receptors, CYFIP2, coatomer alpha. Also, differential editing between neurons and microglia is demonstrated in this work for some of the proteins from primary murine brain cell cultures. Because many edited sites are still not characterized functionally at the protein level, the results provide a necessary background for their further analysis in normal and diseased cells and tissues using targeted proteomic approaches.

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Comparative analysis of A-to-I editing in human and non-human primate brains reveals conserved patterns and context-dependent regulation of RNA editing

Cited by 10 publications

References 24 publications

Large-scale RNA editing profiling in different adult chicken tissues

Large-scale RNA editing profiling in different adult chicken tissues

A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations

Adenosine‐to‐Inosine RNA Editing in Mouse and Human Brain Proteomes

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