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Identification of exceptionally potent adenosine deaminases RNA editors from high body temperature organisms

The 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...

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Autores principales: 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, Shay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019624/
https://www.ncbi.nlm.nih.gov/pubmed/36877730
http://dx.doi.org/10.1371/journal.pgen.1010661
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author 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, Shay
author_facet 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, Shay
author_sort Avram-Shperling, Adi
collection PubMed
description The 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.
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spelling pubmed-100196242023-03-17 Identification of exceptionally potent adenosine deaminases RNA editors from high body temperature organisms 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, Shay PLoS Genet Research Article The 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. Public Library of Science 2023-03-06 /pmc/articles/PMC10019624/ /pubmed/36877730 http://dx.doi.org/10.1371/journal.pgen.1010661 Text en © 2023 Avram-Shperling et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
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, Shay
Identification of exceptionally potent adenosine deaminases RNA editors from high body temperature organisms
title Identification of exceptionally potent adenosine deaminases RNA editors from high body temperature organisms
title_full Identification of exceptionally potent adenosine deaminases RNA editors from high body temperature organisms
title_fullStr Identification of exceptionally potent adenosine deaminases RNA editors from high body temperature organisms
title_full_unstemmed Identification of exceptionally potent adenosine deaminases RNA editors from high body temperature organisms
title_short Identification of exceptionally potent adenosine deaminases RNA editors from high body temperature organisms
title_sort identification of exceptionally potent adenosine deaminases rna editors from high body temperature organisms
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019624/
https://www.ncbi.nlm.nih.gov/pubmed/36877730
http://dx.doi.org/10.1371/journal.pgen.1010661
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