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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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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. |
format | Online Article Text |
id | pubmed-9073681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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