Josephine Davey-Young, Farah Hasan, Rasangi Tennakoon, Peter Rozik, Henry Moore, Peter Hall, Ecaterina Cozma, Julie Genereaux, Kyle S Hoffman, Patricia P Chan, Todd M Lowe, Christopher J Brandl, Patrick O'Donoghue
Translation fidelity relies on accurate aminoacylation of transfer RNAs (tRNAs) by aminoacyl-tRNA synthetases (AARSs). AARSs specific for alanine (Ala), leucine (Leu), serine, and pyrrolysine do not recognize the anticodon bases. Single nucleotide anticodon variants in their cognate tRNAs can lead to mistranslation. Human genomes include both rare and more common mistranslating tRNA variants. We investigated three rare human tRNALeu variants that mis-incorporate Leu at phenylalanine or tryptophan codons. Expression of each tRNALeu anticodon variant in neuroblastoma cells caused defects in fluorescent protein production without significantly increased cytotoxicity under normal conditions or in the context of proteasome inhibition...
January 2024: RNA Biology