Levanon
Erez
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Erez
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PreprintTrade-off between transcriptome plasticity and genome evolution in cephalopods( 2017-03) Liscovitch-Brauer, Noa ; Alon, Shahar ; Porath, Hagit T. ; Elstein, Boaz ; Unger, Ron ; Ziv, Tamar ; Admon, Arie ; Levanon, Erez ; Rosenthal, Joshua J. C. ; Eisenberg, EliRNA editing, a post-transcriptional process, allows the diversification of proteomes beyond the genomic blueprint; however it is infrequently used among animals. Recent reports suggesting increased levels of RNA editing in squids thus raise the question of their nature and effects in these organisms. We here show that RNA editing is particularly common in behaviorally sophisticated coleoid cephalopods, with tens of thousands of evolutionarily conserved sites. Editing is enriched in the nervous system affecting molecules pertinent for excitability and neuronal morphology. The genomic sequence flanking editing sites is highly conserved, suggesting that the process confers a selective advantage. Due to the large number of sites, the surrounding conservation greatly reduces the number of mutations and genomic polymorphisms in protein coding regions. This trade-off between genome evolution and transcriptome plasticity highlights the importance of RNA recoding as a strategy for diversifying proteins, particularly those associated with neural function.
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ArticleA-to-I RNA editing in the earliest-diverging Eumetazoan phyla(Oxford University Press, 2017-04-08) Porath, Hagit T. ; Schaffer, Amos A. ; Kaniewska, Paulina ; Alon, Shahar ; Eisenberg, Eli ; Rosenthal, Joshua J. C. ; Levanon, Erez ; Levy, OrenThe highly conserved ADAR enzymes, found in all multicellular metazoans, catalyze the editing of mRNA transcripts by the deamination of adenosines to inosines. This type of editing has two general outcomes: site specific editing, which frequently leads to recoding, and clustered editing, which is usually found in transcribed genomic repeats. Here, for the first time, we looked for both editing of isolated sites and clustered, non-specific sites in a basal metazoan, the coral Acropora millepora during spawning event, in order to reveal its editing pattern. We found that the coral editome resembles the mammalian one: it contains more than 500,000 sites, virtually all of which are clustered in non-coding regions that are enriched for predicted dsRNA structures. RNA editing levels were increased during spawning and increased further still in newly released gametes. This may suggest that editing plays a role in introducing variability in coral gametes.
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ArticleIdentification of exceptionally potent adenosine deaminases RNA editors from high body temperature organisms(Public Library of Science, 2023-03-06) Avram-Shperling, Adi ; Kopel, Eli ; Twersky, Itamar ; Gabay, Orshay ; Ben-David, Amit ; Karako-Lampert, Sarit ; Rosenthal, Joshua J C ; Levanon, Erez Y ; Eisenberg, Eli ; Ben-Aroya, ShayThe most abundant form of RNA editing in metazoa is the deamination of adenosines into inosines (A-to-I), catalyzed by ADAR enzymes. Inosines are read as guanosines by the translation machinery, and thus A-to-I may lead to protein recoding. The ability of ADARs to recode at the mRNA level makes them attractive therapeutic tools. Several approaches for Site-Directed RNA Editing (SDRE) are currently under development. A major challenge in this field is achieving high on-target editing efficiency, and thus it is of much interest to identify highly potent ADARs. To address this, we used the baker yeast Saccharomyces cerevisiae as an editing-naïve system. We exogenously expressed a range of heterologous ADARs and identified the hummingbird and primarily mallard-duck ADARs, which evolved at 40-42°C, as two exceptionally potent editors. ADARs bind to double-stranded RNA structures (dsRNAs), which in turn are temperature sensitive. Our results indicate that species evolved to live with higher core body temperatures have developed ADAR enzymes that target weaker dsRNA structures and would therefore be more effective than other ADARs. Further studies may use this approach to isolate additional ADARs with an editing profile of choice to meet specific requirements, thus broadening the applicability of SDRE.