Visualizing tRNA-dependent mistranslation in human cells

RNA Biology
Jeremy T LantPatrick O'Donoghue

Abstract

High-fidelity translation and a strictly accurate proteome were originally assumed as essential to life and cellular viability. Yet recent studies in bacteria and eukaryotic model organisms suggest that proteome-wide mistranslation can provide selective advantages and is tolerated in the cell at higher levels than previously thought (one error in 6.9 × 10-4 in yeast) with a limited impact on phenotype. Previously, we selected a tRNAPro containing a single mutation that induces mistranslation with alanine at proline codons in yeast. Yeast tolerate the mistranslation by inducing a heat-shock response and through the action of the proteasome. Here we found a homologous human tRNAPro (G3:U70) mutant that is not aminoacylated with proline, but is an efficient alanine acceptor. In live human cells, we visualized mistranslation using a green fluorescent protein reporter that fluoresces in response to mistranslation at proline codons. In agreement with measurements in yeast, quantitation based on the GFP reporter suggested a mistranslation rate of up to 2-5% in HEK 293 cells. Our findings suggest a stress-dependent phenomenon where mistranslation levels increased during nutrient starvation. Human cells did not mount a detectable heat-s...Continue Reading

References

Jan 16, 2019·The Journal of Biological Chemistry·Jeremy T LantPatrick O'Donoghue
Aug 14, 2019·RNA Biology·Matthew D BergChristopher J Brandl
Sep 6, 2019·Genetics·Matthew D BergChristopher J Brandl
Sep 10, 2020·RNA Biology·Matthew D Berg, Christopher J Brandl
Jun 2, 2020·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Yanrui ZhuChrisopher J Brandl
Aug 14, 2018·RNA Biology·Patrick O'DonoghueDieter Söll
Oct 22, 2020·G3 : Genes - Genomes - Genetics·Matthew D BergChristopher J Brandl

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Related Concepts

Fluorescent Dyes
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