Eugene Bell Center for Regenerative Biology and Tissue Engineering

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https://hdl.handle.net/1912/4819

The ability of many animals to spontaneously regenerate their body parts has intrigued scientific observers for centuries. Although humans share the same basic genes and pathways, we have somehow lost these regenerative capacities, which leads to significant health costs. An understanding of tissue and organ regeneration in lower animals holds great promise for translating to medical treatments for serious human conditions, including spinal cord injury, diabetes, organ failure, and degenerative neural diseases such as Alzheimer’s.

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Browsing Eugene Bell Center for Regenerative Biology and Tissue Engineering by Subject "ADAR"
  • Article
    A-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, Oren
    The 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.
  • Article
    Extensive recoding of the neural proteome in cephalopods by RNA editing
    (Annual Reviews, 2023-02) Rosenthal, Joshua J.C. ; Eisenberg, Eli
    The coleoid cephalopods have the largest brains, and display the most complex behaviors, of all invertebrates. The molecular and cellular mechanisms that underlie these remarkable advancements remain largely unexplored. Early molecular cloning studies of squid ion channel transcripts uncovered an unusually large number of A?I RNA editing sites that recoded codons. Further cloning of other neural transcripts showed a similar pattern. The advent of deep-sequencing technologies and the associated bioinformatics allowed the mapping of RNA editing events across the entire neural transcriptomes of various cephalopods. The results were remarkable: They contained orders of magnitude more recoding editing sites than any other taxon. Although RNA editing sites are abundant in most multicellular metazoans, they rarely recode. In cephalopods, the majority of neural transcripts are recoded. Recent studies have focused on whether these events are adaptive, as well as other noncanonical aspects of cephalopod RNA editing.
  • Article
    Squid express conserved ADAR orthologs that possess novel features
    (Frontiers Media, 2023-06-05) Vallecillo-Viejo, Isabel C. ; Voss, Gjendine ; Albertin, Caroline B. ; Liscovitch-Brauer, Noa ; Eisenberg, Eli ; Rosenthal, Joshua J. C.
    The coleoid cephalopods display unusually extensive mRNA recoding by adenosine deamination, yet the underlying mechanisms are not well understood. Because the adenosine deaminases that act on RNA (ADAR) enzymes catalyze this form of RNA editing, the structure and function of the cephalopod orthologs may provide clues. Recent genome sequencing projects have provided blueprints for the full complement of coleoid cephalopod ADARs. Previous results from our laboratory have shown that squid express an ADAR2 homolog, with two splice variants named sqADAR2a and sqADAR2b and that these messages are extensively edited. Based on octopus and squid genomes, transcriptomes, and cDNA cloning, we discovered that two additional ADAR homologs are expressed in coleoids. The first is orthologous to vertebrate ADAR1. Unlike other ADAR1s, however, it contains a novel N-terminal domain of 641 aa that is predicted to be disordered, contains 67 phosphorylation motifs, and has an amino acid composition that is unusually high in serines and basic amino acids. mRNAs encoding sqADAR1 are themselves extensively edited. A third ADAR-like enzyme, sqADAR/D-like, which is not orthologous to any of the vertebrate isoforms, is also present. Messages encoding sqADAR/D-like are not edited. Studies using recombinant sqADARs suggest that only sqADAR1 and sqADAR2 are active adenosine deaminases, both on perfect duplex dsRNA and on a squid potassium channel mRNA substrate known to be edited in vivo. sqADAR/D-like shows no activity on these substrates. Overall, these results reveal some unique features in sqADARs that may contribute to the high-level RNA recoding observed in cephalopods.
  • Preprint
    Trade-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, Eli
    RNA 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.