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

Levitsky, Lev I.; Kliuchnikova, Anna A.; Kuznetsova, Ksenia G.; Карпов, Д. С.; Ivanov, Mark V.; Pyatnitskiy, Mikhail A.; Kalinina, Olga; Gorshkov, Mikhail V.; Moshkovskii, Sergei A.

doi:10.1002/pmic.201900195

Cited by 18 publications

(38 citation statements)

References 73 publications

(166 reference statements)

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“…Generally, in fruit flies, coding editing events occur at higher rates than in humans and mice, which was shown at both transcriptome [14,15] and proteome [16,17] levels. This fact, at least partially, can be explained by the need for profound morphological and physiological changes in the insect which experiences a metamorphosis during its lifespan.…”

Section: Introductionmentioning

confidence: 99%

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Proteome-Wide Analysis of ADAR-Mediated Messenger RNA Editing during Fruit Fly Ontogeny

et al. 2020

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Highlights• Proteogenomic approach was applied to shotgun proteomics data of fruit fly ontogeny for identification of proteoforms originating from adenosine-to-inosine RNA editing.• Edited proteins identified at all life cycle stages are enriched in annotated protein-protein interactions at statistically significant level with many of them associated with actomyosin and synaptic vesicle functions.• Proteome-wide RNA editing event profiles were found specific to life cycle phase and independent of the protein abundances..

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Section: Introductionmentioning

confidence: 99%

“…Coding RNA editing events in mRNA were mostly studied in transcripts [22], and only a few works used mass-spectrometry data to identify amino acid substitutions generated by transcriptome-wide ADAR activity. This was studied for human cancers [21], murine and human brains [17], as well as fruit fly's body, head and brain [16].…”

Section: Introductionmentioning

confidence: 99%

Proteome-Wide Analysis of ADAR-Mediated Messenger RNA Editing during Fruit Fly Ontogeny

et al. 2020

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“…RNA editing is the post-transcriptional or co-transcriptional process which could make transcripts more complicated and results in potential functional consequences [ 1 , 2 ]. RNA editing sites have been found in different vertebrates, including humans [ 3 , 4 , 5 , 6 ], mice [ 4 ], pigs [ 1 , 7 , 8 ], bovines [ 9 ], and chickens [ 10 ]. The RNA editing events were usually catalyzed by adenosine deaminase RNA specific (ADAR), and represent the form of A-to-I in mammals [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, RNA editing sites in intergenic region may associated with nuclear retention [ 15 ], and in introns may disrupt alternative splicing [ 16 ]. In humans, RNA editing is associated with disease [ 3 , 4 , 5 ]; in animals, RNA editing was found to be associated with embryo and tissue development [ 1 ], production traits [ 17 ], and Newcastle disease virus [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Identification of RNA Editing Sites Affecting Intramuscular Fat in Pigs

Wang

Hou

et al. 2020

Animals

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Intramuscular fat (IMF) is essential for improving the palatability and flavor of meat, and it is strongly associated with human insulin resistance. RNA editing is a widespread regulating event in different tissues. Here, we investigated the global RNA editing difference of two groups of pig with different IMF contents to find the potential editing sites affecting IMF. In this research, RES-Scanner and REDItools were used to identify RNA editing sites based on the whole genome and transcriptome sequencing data of the high and low groups composed of three full-sib pairs with opposite IMF phenotypes. A total of 295 RNA editing sites were investigated in the longissimus dorsi muscle, and 90.17% of these sites caused A to G conversion. After annotation, most editing sites were located in noncoding regions (including five sites located on the 3′ UTR regions). Five editing sites (including two sites that could lead to nonsynonymous amino acid changes) were located in the exons of genes. A total of 36 intergroup (high and low IMF) differential RNA editing sites were found in 33 genes. Some candidate editing sites, such as sites in acyl-coenzymeA: cholesterol acyltransferase 1 (ACAT1), coatomer protein, subunit alpha (COPA), and nuclear receptor coactivator 3 (NCOA3), were selected as candidate RNA editing sites associated with IMF. One site located on the 3′ UTR region of growth hormone secretagogue receptor (GHSR) may regulate GHSR expression by affecting the interaction of miRNA and mRNA. In conclusion, we identified a total of 36 nonredundant RNA editing sites in the longissimus dorsi muscle, which may reveal the potential importance of RNA editing in IMF. Four were selected as candidate sites associated with IMF. Our findings provide some new insights of RNA editing function in pig longissimus dorsi muscle which useful for pig IMF breeding or human insulin resistances research.

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Section: Introductionmentioning

confidence: 99%

Proteome-Wide Analysis of ADAR-mediated Messenger RNA Editing During Fruit Fly Ontogeny

Kliuchnikova

Goncharov

Levitsky

et al. 2020

Preprint

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Moshkovskii S.A.). Highlights• Proteogenomic approach was applied to shotgun proteomics data of fruit fly ontogeny for identification of proteoforms originating from adenosine-to-inosine RNA editing.• Edited proteins identified at all life cycle stages are enriched in annotated protein-protein interactions at statistically significant level with many of them associated with actomyosin and synaptic vesicle functions.• Proteome-wide RNA editing event profiles were found specific to life cycle phase and independent of the protein abundances.• A majority of RNA editing events at the protein level was observed after metamorphosis in late pupae to adult insects, which was consistent with transcriptome data.• Targeted proteomic analysis of five selected edited sites and their genomic counterparts in brains for three phases of the fruit fly life cycle have demonstrated a clear increase in editing rate of up to 80% for the endophilin A protein in adult flies. AbstractAdenosine-to-inosine RNA editing is an enzymatic post-transcriptional modification which modulates immunity and neural transmission in multicellular organisms. Some of its functions are enforced through editing of mRNA codons with the resulting amino acid substitutions. We identified these sites originated from the RNA editing for developmental proteomes of Drosophila melanogaster at the protein level using available proteomic data for fifteen stages of fruit fly development from egg to imago and fourteen time points of embryogenesis. In total, 42 sites each belonging to a unique protein were found including four sites related to embryogenesis. The interactome analysis has revealed that most of the edited proteins are associated with synaptic vesicle trafficking and actomyosin organization. Quantitation data analysis suggested the existence of phase-specific RNA editing regulation by yet unknown mechanisms. These results support transcriptome analyses showing that a burst in RNA editing occurs during insect metamorphosis from pupa to imago. Further, targeted proteomics was employed to quantify edited and genomically encoded versions of five proteins in brains of larvae, pupae, and imago insects showing a clear trend towards an increase in editing rate for all of them. Our results may help to reveal the protein functions in physiological effects of RNA editing. SignificanceAdenosine-to-inosine RNA editing has multiple effects on body functions in many multicellular organisms from insects and molluscs to humans. Recent studies show that at least some of these effects are mediated by changes in protein sequences due to editing of codons in mRNA. However, it is not known how exactly the edited proteins can participate in RNA editing-mediated pathways.Moreover, most studies of edited proteins are based on the deduction of protein sequence changes from analysis of transcriptome without measurements of proteins themselves. Earlier, we explored for the first time the edited proteins of Drosophila melanogaster proteome. In this work, we continued the proteome-wide ana...

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

Cited by 18 publications

References 73 publications

Proteome-Wide Analysis of ADAR-Mediated Messenger RNA Editing during Fruit Fly Ontogeny

Proteome-Wide Analysis of ADAR-Mediated Messenger RNA Editing during Fruit Fly Ontogeny

Genome-Wide Identification of RNA Editing Sites Affecting Intramuscular Fat in Pigs

Proteome-Wide Analysis of ADAR-mediated Messenger RNA Editing During Fruit Fly Ontogeny

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