Current Biology
Volume 28, Issue 13, 9 July 2018, Pages 2046-2057.e5
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Article
Endogenous Stochastic Decoding of the CUG Codon by Competing Ser- and Leu-tRNAs in Ascoidea asiatica

https://doi.org/10.1016/j.cub.2018.04.085Get rights and content
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Highlights

  • Ascoidea asiatica stochastically encodes CUG as leucine and serine

  • It is the only known example of a proteome with non-deterministic features

  • Stochastic encoding is caused by competing tRNALeu(CAG) and tRNASer(CAG)

  • A. asiatica copes with stochastic encoding by avoiding CUG at key positions

Summary

Although the “universal” genetic code is now known not to be universal, and stop codons can have multiple meanings, one regularity remains, namely that for a given sense codon there is a unique translation. Examining CUG usage in yeasts that have transferred CUG away from leucine, we here report the first example of dual coding: Ascoidea asiatica stochastically encodes CUG as both serine and leucine in approximately equal proportions. This is deleterious, as evidenced by CUG codons being rare, never at conserved serine or leucine residues, and predominantly in lowly expressed genes. Related yeasts solve the problem by loss of function of one of the two tRNAs. This dual coding is consistent with the tRNA-loss-driven codon reassignment hypothesis, and provides a unique example of a proteome that cannot be deterministically predicted.

Keywords

genetic code
codon reassignment
stochastic decoding
competing tRNAs
CUG codon
Ascoidea asiatica
Saccharomycopsis
yeast evolution
proteomics

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