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Mistranslating tRNA variants have anticodon- and sex-specific impacts on Drosophila melanogaster.
Isaacson, Joshua R; Berg, Matthew D; Jagiello, Jessica; Yeung, William; Charles, Brendan; Villén, Judit; Brandl, Christopher J; Moehring, Amanda J.
Afiliación
  • Isaacson JR; Department of Biology, Western University, N6A 5B7, London, Canada.
  • Berg MD; Department of Genome Sciences, University of Washington, Seattle, Washington, 98195.
  • Jagiello J; Department of Biology, Western University, N6A 5B7, London, Canada.
  • Yeung W; Department of Biology, Western University, N6A 5B7, London, Canada.
  • Charles B; Department of Biology, Western University, N6A 5B7, London, Canada.
  • Villén J; Department of Genome Sciences, University of Washington, Seattle, Washington, 98195.
  • Brandl CJ; Department of Biochemistry, Western University, N6A 5B7, London, Canada.
  • Moehring AJ; Department of Biology, Western University, N6A 5B7, London, Canada.
bioRxiv ; 2024 Jun 13.
Article en En | MEDLINE | ID: mdl-38915589
ABSTRACT
Transfer RNAs (tRNAs) are vital in determining the specificity of translation. Mutations in tRNA genes can result in the misincorporation of amino acids into nascent polypeptides in a process known as mistranslation. Since mistranslation has different impacts, depending on the type of amino acid substitution, our goal here was to compare the impact of different mistranslating tRNASer variants on fly development, lifespan, and behaviour. We established two mistranslating fly lines, one with a tRNASer variant that misincorporates serine at valine codons (V→S) and the other that misincorporates serine at threonine codons (T→S). While both mistranslating tRNAs increased development time and developmental lethality, the severity of the impacts differed depending on amino acid substitution and sex. The V→S variant extended embryonic, larval, and pupal development whereas the T→S only extended larval and pupal development. Females, but not males, containing either mistranslating tRNA presented with significantly more anatomical deformities than controls. Mistranslating females also experienced extended lifespan whereas mistranslating male lifespan was unaffected. In addition, mistranslating flies from both sexes showed improved locomotion as they aged, suggesting delayed neurodegeneration. Therefore, although mistranslation causes detrimental effects, we demonstrate that mistranslation also has positive effects on complex traits such as lifespan and locomotion. This has important implications for human health given the prevalence of tRNA variants in humans.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos