Varied forms of mutant tRNA mistranslation produce distinct phenotypes across multiple model organisms

Mutant tRNA mistranslation in multiple model organisms shows that toxicity is often linked to large biochemical shifts between exchanged amino acids and higher mistranslation frequency, with notable exceptions.

• Why it matters: Outcomes of mistranslating tRNAs are context-dependent, and it is unclear which tRNA-specific features best predict deleterious phenotypes versus more product-specific mechanisms.
• What they did: The authors built a curated array of tRNA mutants and assessed how amino-acid biochemical differences and mistranslation frequency relate to phenotype severity, including mass spectrometry quantification of mistranslated products.
• The result: Toxic phenotypes show a weak relationship between the amount of mistranslated products and severity, and in Drosophila melanogaster higher-frequency variants were largely unsuccessful while lower-frequency variants produced no detectable developmental phenotypes.

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