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A novel mistranslating tRNA model in Drosophila melanogaster has diverse, sexually dimorphic effects

Transfer RNAs (tRNAs) are the adaptor molecules required for reading the genetic code and producing proteins. Transfer RNA variants can lead to genome-wide mistranslation, the misincorporation of amino acids not specified by the standard genetic code into nascent proteins. While genome sequencing ha...

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Autores principales: Isaacson, Joshua R, Berg, Matthew D, Charles, Brendan, Jagiello, Jessica, Villén, Judit, Brandl, Christopher J, Moehring, Amanda J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9073681/
https://www.ncbi.nlm.nih.gov/pubmed/35143655
http://dx.doi.org/10.1093/g3journal/jkac035
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author Isaacson, Joshua R
Berg, Matthew D
Charles, Brendan
Jagiello, Jessica
Villén, Judit
Brandl, Christopher J
Moehring, Amanda J
author_facet Isaacson, Joshua R
Berg, Matthew D
Charles, Brendan
Jagiello, Jessica
Villén, Judit
Brandl, Christopher J
Moehring, Amanda J
author_sort Isaacson, Joshua R
collection PubMed
description Transfer RNAs (tRNAs) are the adaptor molecules required for reading the genetic code and producing proteins. Transfer RNA variants can lead to genome-wide mistranslation, the misincorporation of amino acids not specified by the standard genetic code into nascent proteins. While genome sequencing has identified putative mistranslating transfer RNA variants in human populations, little is known regarding how mistranslation affects multicellular organisms. Here, we create a multicellular model of mistranslation by integrating a serine transfer RNA variant that mistranslates serine for proline ([Formula: see text]) into the Drosophila melanogaster genome. We confirm mistranslation via mass spectrometry and find that [Formula: see text] misincorporates serine for proline at a frequency of ∼0.6% per codon. [Formula: see text] extends development time and decreases the number of flies that reach adulthood. While both sexes of adult flies containing [Formula: see text] present with morphological deformities and poor climbing performance, these effects are more pronounced in female flies and the impact on climbing performance is exacerbated by age. This model will enable studies into the synergistic effects of mistranslating transfer RNA variants and disease-causing alleles.
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spelling pubmed-90736812022-05-06 A novel mistranslating tRNA model in Drosophila melanogaster has diverse, sexually dimorphic effects Isaacson, Joshua R Berg, Matthew D Charles, Brendan Jagiello, Jessica Villén, Judit Brandl, Christopher J Moehring, Amanda J G3 (Bethesda) Investigation Transfer RNAs (tRNAs) are the adaptor molecules required for reading the genetic code and producing proteins. Transfer RNA variants can lead to genome-wide mistranslation, the misincorporation of amino acids not specified by the standard genetic code into nascent proteins. While genome sequencing has identified putative mistranslating transfer RNA variants in human populations, little is known regarding how mistranslation affects multicellular organisms. Here, we create a multicellular model of mistranslation by integrating a serine transfer RNA variant that mistranslates serine for proline ([Formula: see text]) into the Drosophila melanogaster genome. We confirm mistranslation via mass spectrometry and find that [Formula: see text] misincorporates serine for proline at a frequency of ∼0.6% per codon. [Formula: see text] extends development time and decreases the number of flies that reach adulthood. While both sexes of adult flies containing [Formula: see text] present with morphological deformities and poor climbing performance, these effects are more pronounced in female flies and the impact on climbing performance is exacerbated by age. This model will enable studies into the synergistic effects of mistranslating transfer RNA variants and disease-causing alleles. Oxford University Press 2022-02-10 /pmc/articles/PMC9073681/ /pubmed/35143655 http://dx.doi.org/10.1093/g3journal/jkac035 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America. 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 reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigation
Isaacson, Joshua R
Berg, Matthew D
Charles, Brendan
Jagiello, Jessica
Villén, Judit
Brandl, Christopher J
Moehring, Amanda J
A novel mistranslating tRNA model in Drosophila melanogaster has diverse, sexually dimorphic effects
title A novel mistranslating tRNA model in Drosophila melanogaster has diverse, sexually dimorphic effects
title_full A novel mistranslating tRNA model in Drosophila melanogaster has diverse, sexually dimorphic effects
title_fullStr A novel mistranslating tRNA model in Drosophila melanogaster has diverse, sexually dimorphic effects
title_full_unstemmed A novel mistranslating tRNA model in Drosophila melanogaster has diverse, sexually dimorphic effects
title_short A novel mistranslating tRNA model in Drosophila melanogaster has diverse, sexually dimorphic effects
title_sort novel mistranslating trna model in drosophila melanogaster has diverse, sexually dimorphic effects
topic Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9073681/
https://www.ncbi.nlm.nih.gov/pubmed/35143655
http://dx.doi.org/10.1093/g3journal/jkac035
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