Massive A-to-I RNA editing is common across the Metazoa and correlates with dsRNA abundance

Porath, Hagit T.; Knisbacher, Binyamin A.; Eisenberg, Eli; Levanon, Erez Y.

doi:10.1186/s13059-017-1315-y

Cited by 142 publications

(144 citation statements)

References 60 publications

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“…We identified many novel editing sites in these neuronal populations. These novel sites, which were often found in lowly expressed transcripts, mostly overlapped repetitive regions of the transcriptome and contained numerous editing sites, which is consistent with previous reports of editing of repeat regions in flies and many other species including Alu sequences in human 52,53 .…”

Section: Discussionsupporting

confidence: 90%

Illuminating spatial A-to-I RNA editing signatures within the Drosophila brain

Sapiro

Shmueli

Henry

et al. 2018

Preprint

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Significance StatementA fundamental question in contemporary neuroscience is how the remarkable cellular diversity required for the intricate function of the nervous system is achieved. In this manuscript, we bridge the gap between a cellular machinery that is known to diversify the transcriptome and the existence of distinct neuronal populations that compose Drosophila brain. Adenosine-to-inosine (A-to-I) RNA-editing is a ubiquitous mechanism that generates transcriptomic diversity in cells by recoding certain adenosines within the pre-mRNA sequence into inosines. We present a spatial map of RNA editing across different neuronal populations in Drosophila brain. Each neuronal population has a distinct editing signature, with the majority of differential editing occurring in highly conserved regions of transcripts that encode ion channels and other essential neuronal genes.

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Section: Discussionsupporting

confidence: 90%

Illuminating spatial A-to-I RNA editing signatures within the Drosophila brain

Sapiro

Shmueli

Henry

et al. 2018

Preprint

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“…The use of RNA editing as a tool for brain development was important for these groups, but ultimately limited by the aforementioned costs. The deployment of RNA editing was largely limited to non-coding edits ( 68,69 ) in order to limit the load of potentially damaging proteins with off-target recoding events. Cephalopods faced very different evolutionary pressures during their evolution.…”

Section: Discussionmentioning

confidence: 99%

Evolutionary Analyses of RNA Editing and Amino Acid Recoding in Cephalopods

Wang

Mohlhenrich

2019

Preprint

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RNA editing is a post-transcriptional modification process that alters nucleotides of mRNA and consequently the amino acids of the translated protein without changing the original DNA sequence. In human and other mammals, amino acid recoding from RNA editing is rare, and most edits are non-adaptive and provide no fitness advantage ( 1 ). However, recently it was discovered that in soft-bodied cephalopods, which are exceptionally intelligent and include squid, octopus, and cuttlefish, RNA editing is widespread and positively selected ( 2 ). To examine the effects of RNA editing on individual genes, we developed a "diversity score" system that quantitatively assesses the amount of diversity generated in each gene, incorporating combinatorial diversity and the radicalness of amino acid changes. Using this metric, we compiled a list of top 100 genes across the cephalopod species that are most diversified by RNA editing. This list of candidate genes provides directions for future research into the specific functional impact of RNA editing in terms of protein structure and cellular function on individual proteins. Additionally, considering the connection of RNA editing to the nervous system, and the exceptional intelligence of cephalopod, the candidate genes may shed light to the molecular development of behavioral complexity and intelligence. To further investigate global influences of RNA editing on the transcriptome, we investigated changes in nucleotide composition and codon usage biases in edited genes and coleoid transcriptome in general. Results show that these features indeed correlate with editing and may correspond to causes or effects of RNA editing. In addition, we characterized the unusual RNA editing in cephalopods by analyzing ratio of radical to conservative amino acid substitutions (R/C) and distribution of amino acid recoding from editing. Our results show that compared to model organisms, editing in cephalopods have significantly decreased R/C ratio and distinct distribution of amino acid substitutions that favor conservative over radical changes, indicating selection at the amino acid level and providing a potential mechanism for the evolution of widespread RNA editing in cephalopods.

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“…Only 20 of the hibernation edited sites with either pattern lie within coding regions, and just 12 of these would recode the corresponding protein. Instead, the vast majority of the edited sites reside in SINE-family interspersed repeats, as is typical of non-hibernating, homeothermic mammals (Porath et al 2017a) .…”

Section: Discussionmentioning

confidence: 99%

Dynamic temperature-sensitive A-to-I RNA editing in the brain of a heterothermic mammal during hibernation

Riemondy

Gillen

White

et al. 2018

Preprint

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RNA editing diversifies genomically encoded information to expand the complexity of the transcriptome. In ectothermic organisms, including Drosophila and Cephalopoda , where body temperature mirrors ambient temperature, decreases in environmental temperature lead to increases in A-to-I RNA editing and cause amino acid recoding events that are thought to be adaptive responses to temperature fluctuations. In contrast, endothermic mammals, including humans and mice, typically maintain a constant body temperature despite environmental changes. Here, A-to-I editing primarily targets repeat elements, rarely results in the recoding of amino acids and plays a critical role in innate immune tolerance. Hibernating ground squirrels provide a unique opportunity to examine RNA editing in a heterothermic mammal whose body temperature varies over 30°C and can be maintained at 5°C for many days during torpor. We profiled the transcriptome in three brain regions at six physiological states to quantify RNA editing and determine whether cold-induced RNA editing modifies the transcriptome as a potential mechanism for neuroprotection at low temperature during hibernation. We identified 5,165 A-to-I editing sites in 1,205 genes with dynamically increased editing after prolonged cold exposure. The majority (99.6%) of the cold-increased editing sites are outside of previously annotated coding regions, 82.7% lie in SINE-derived repeats, and 12 sites are predicted to recode amino acids. Additionally, A-to-I editing frequencies increase with increasing cold-exposure demonstrating that ADAR remains active during torpor. Our findings suggest that dynamic A-to-I editing at low body temperature may provide a neuroprotective mechanism to limit aberrant dsRNA accumulation during torpor in the mammalian hibernator.

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Massive A-to-I RNA editing is common across the Metazoa and correlates with dsRNA abundance

Cited by 142 publications

References 60 publications

Illuminating spatial A-to-I RNA editing signatures within the Drosophila brain

Illuminating spatial A-to-I RNA editing signatures within the Drosophila brain

Evolutionary Analyses of RNA Editing and Amino Acid Recoding in Cephalopods

Dynamic temperature-sensitive A-to-I RNA editing in the brain of a heterothermic mammal during hibernation

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