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Versatility of Synthetic tRNAs in Genetic Code Expansion

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
Department of Chemistry, Yale University, New Haven, CT 06520, USA
Author to whom correspondence should be addressed.
Genes 2018, 9(11), 537;
Received: 16 October 2018 / Revised: 31 October 2018 / Accepted: 5 November 2018 / Published: 7 November 2018
(This article belongs to the Special Issue Synthetic DNA and RNA Programming)
PDF [1012 KB, uploaded 7 November 2018]


Transfer RNA (tRNA) is a dynamic molecule used by all forms of life as a key component of the translation apparatus. Each tRNA is highly processed, structured, and modified, to accurately deliver amino acids to the ribosome for protein synthesis. The tRNA molecule is a critical component in synthetic biology methods for the synthesis of proteins designed to contain non-canonical amino acids (ncAAs). The multiple interactions and maturation requirements of a tRNA pose engineering challenges, but also offer tunable features. Major advances in the field of genetic code expansion have repeatedly demonstrated the central importance of suppressor tRNAs for efficient incorporation of ncAAs. Here we review the current status of two fundamentally different translation systems (TSs), selenocysteine (Sec)- and pyrrolysine (Pyl)-TSs. Idiosyncratic requirements of each of these TSs mandate how their tRNAs are adapted and dictate the techniques used to select or identify the best synthetic variants. View Full-Text
Keywords: genetic code expansion; transfer RNA; synthetic biology; non-canonical amino acids; selenocysteine genetic code expansion; transfer RNA; synthetic biology; non-canonical amino acids; selenocysteine

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Hoffman, K.S.; Crnković, A.; Söll, D. Versatility of Synthetic tRNAs in Genetic Code Expansion. Genes 2018, 9, 537.

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