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Repurposing tRNAs for nonsense suppression by Suki Albers; Bertrand Beckert; Marco C. Matthies; Chandra Sekhar Mandava; Raphael Schuster; Carolin Seuring; Maria Riedner; Suparna Sanyal; Andrew E. Torda; Daniel N. Wilson; Zoya Ignatova is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Repurposing tRNAs for nonsense suppression about?

Three stop codons (UAA, UAG and UGA) terminate protein synthesis and are almost exclusively recognized by release factors. Here, we design de novo transfer RNAs (tRNAs) that efficiently decode UGA stop codons in __Escherichia coli__. The tRNA designs harness various functionally conserved aspects of sense-codon decoding tRNAs. Optimization within the TΨC-stem to stabilize binding to the elongation factor, displays the most potent effect in enhancing suppression activity. We determine the structure of the ribosome in a complex with the designed tRNA bound to a UGA stop codon in the A site at 2.9 Å resolution. In the context of the suppressor tRNA, the conformation of the UGA codon resembles that of a sense-codon rather than when canonical translation termination release factors are bound, suggesting conformational flexibility of the stop codons dependent on the nature of the A-site ligand. The systematic analysis, combined with structural insights, provides a rationale for targeted repurposing of tRNAs to correct devastating nonsense mutations that introduce a premature stop codon.

Who reads Repurposing tRNAs for nonsense suppression?

Author

Suki Albers; Bertrand Beckert; Marco C. Matthies; Chandra Sekhar Mandava; Raphael Schuster; Carolin Seuring; Maria Riedner; Suparna Sanyal; Andrew E. Torda; Daniel N. Wilson; Zoya Ignatova

Publisher

Springer Science and Business Media LLC

Published

2021

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)