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Title: RNA-editing enzymes ADAR1 and ADAR2 coordinately regulate the editing and expression of Ctn RNA
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Author(s) / Creator(s):
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Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
FEBS Letters
Page Range / eLocation ID:
2890 to 2904
Medium: X
Sponsoring Org:
National Science Foundation
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  1. Summary

    Hornworts are crucial to understand the phylogeny of early land plants. The emergence of ‘reverse’ U‐to‐C RNA editing accompanying the widespread C‐to‐U RNA editing in plant chloroplasts and mitochondria may be a molecular synapomorphy of a hornwort–tracheophyte clade. C‐to‐U RNA editing is well understood after identification of many editing factors in models likeArabidopsis thalianaandPhyscomitrella patens, but there is no plant model yet to investigate U‐to‐C RNA editing. The hornwortAnthoceros agrestisis now emerging as such a model system.

    We report on the assembly and analyses of theA. agrestischloroplast and mitochondrial genomes, their transcriptomes and editomes, and a large nuclear gene family encoding pentatricopeptide repeat (PPR) proteins likely acting as RNA editing factors.

    Both organelles inA. agrestisfeature high amounts of RNA editing, with altogether > 1100 sites of C‐to‐U and 1300 sites of U‐to‐C editing. The nuclear genome reveals > 1400 genes for PPR proteins with variable carboxyterminal DYW domains.

    We observe significant variants of the ‘classic’ DYW domain, in the meantime confirmed as the cytidine deaminase for C‐to‐U editing, and discuss the first attractive candidates for reverse editing factors given their excellent matches to U‐to‐C editing targets according to the PPR‐RNA binding code.

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  2. Abstract

    Plastid and mitochondrial RNAs in vascular plants are subjected to cytidine‐to‐uridine editing. The model plant speciesArabidopsis thaliana(Arabidopsis) has two nuclear‐encoded plastid‐targeted organelle RNA recognition motif (ORRM) proteins: ORRM1 and ORRM6. In theorrm1mutant, 21 plastid RNA editing sites were affected but none are essential to photosynthesis. In theorrm6mutants, two plastid RNA editing sites were affected:psbF‐C77 andaccD‐C794. BecausepsbFencodes the β subunit of cytochromeb559in photosystem II, which is essential to photosynthesis, theorrm6mutants were much smaller than the wild type. In addition, theorrm6mutants had pale green leaves and reduced photosynthetic efficiency. To investigate the functional relationship between ORRM1 and ORRM6, we generatedorrm1 orrm6double homozygous mutants. Morphological and physiological analyses showed that theorrm1 orrm6double mutants had a smaller plant size, reduced chlorophyll contents, and decreased photosynthetic efficiency, similar to theorrm6single mutants. Although theorrm1 orrm6double mutants adopted the phenotype of theorrm6single mutants, the total number of plastid RNA editing sites affected in theorrm1 orrm6double mutants was the sum of the sites affected in theorrm1andorrm6single mutants. These data suggest that ORRM1 and ORRM6 are in charge of distinct sets of plastid RNA editing sites and that simultaneous mutations inORRM1andORRM6genes do not cause additional reduction in editing extent at other plastid RNA editing sites.

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  3. Lin, Xiaorong (Ed.)
    ABSTRACT Adenosine-to-inosine (A-to-I) RNA editing independent of adenosine deaminase acting on RNA (ADAR) enzymes was discovered in fungi recently, and shown to be crucial for sexual reproduction. However, the underlying mechanism for editing is unknown. Here, we combine genome-wide comparisons, proof-of-concept experiments, and machine learning to decipher cis -regulatory elements of A-to-I editing in Fusarium graminearum . We identified plenty of RNA primary sequences and secondary structural features that affect editing specificity and efficiency. Although hairpin loop structures contribute importantly to editing, unlike in animals, the primary sequences have more profound influences on editing than secondary structures. Nucleotide preferences at adjacent positions of editing sites are the most important features, especially preferences at the −1 position. Unexpectedly, besides the number of positions with preferred nucleotides, the combination of preferred nucleotides with depleted ones at different positions are also important for editing. Some cis -sequence features have distinct importance for editing specificity and efficiency. Machine learning models built from diverse sequence and secondary structural features can accurately predict genome-wide editing sites but not editing levels, indicating that the cis -regulatory principle of editing efficiency is more complex than that of editing specificity. Nevertheless, our model interpretation provides insights into the quantitative contribution of each feature to the prediction of both editing sites and levels. We found that efficient editing of FG3G34330 transcripts depended on the full-length RNA molecule, suggesting that additional RNA structural elements may also contribute to editing efficiency. Our work uncovers multidimensional cis -regulatory elements important for A-to-I RNA editing in F. graminearum , helping to elucidate the fungal editing mechanism. IMPORTANCE A-to-I RNA editing is a new epigenetic phenomenon that is crucial for sexual reproduction in fungi. Deciphering cis -regulatory elements of A-to-I RNA editing can help us elucidate the editing mechanism and develop a model that accurately predicts RNA editing. In this study, we discovered multiple RNA sequence and secondary structure features important for A-to-I editing in Fusarium graminearum . We also identified the cis -sequence features with distinct importance for editing specificity and efficiency. The potential importance of full-length RNA molecules for editing efficiency is also revealed. This study represents the first comprehensive investigation of the cis -regulatory principles of A-to-I RNA editing in fungi. 
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  4. Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by ADAR enzymes, is a ubiquitous mechanism that generates transcriptomic diversity. This process is particularly important for proper neuronal function; however, little is known about how RNA editing is dynamically regulated between the many functionally distinct neuronal populations of the brain. Here, we present a spatial RNA editing map in theDrosophilabrain and show that different neuronal populations possess distinct RNA editing signatures. After purifying and sequencing RNA from genetically marked groups of neuronal nuclei, we identified a large number of editing sites and compared editing levels in hundreds of transcripts across nine functionally different neuronal populations. We found distinct editing repertoires for each population, including sites in repeat regions of the transcriptome and differential editing in highly conserved and likely functional regions of transcripts that encode essential neuronal genes. These changes are site-specific and not driven by changes inAdarexpression, suggesting a complex, targeted regulation of editing levels in key transcripts. This fine-tuning of the transcriptome between different neurons by RNA editing may account for functional differences between distinct populations in the brain.

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