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Title: Versatility of Synthetic tRNAs in Genetic Code Expansion

Abstract

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.

Authors:
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1]
  1. Yale Univ., New Haven, CT (United States)
Publication Date:
Research Org.:
Yale Univ., New Haven, CT (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences, and Biosciences Division; National Science Foundation (NSF); National Institutes of Health (NIH)
OSTI Identifier:
1610398
Grant/Contract Number:  
FG02-98ER20311; CHE-1740549; R35GM122560
Resource Type:
Accepted Manuscript
Journal Name:
Genes
Additional Journal Information:
Journal Volume: 9; Journal Issue: 11; Journal ID: ISSN 2073-4425
Publisher:
MDPI
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; genetic code expansion; transfer RNA; synthetic biology; non-canonical amino acids; selenocysteine

Citation Formats

Hoffman, Kyle, Crnković, Ana, and Söll, Dieter. Versatility of Synthetic tRNAs in Genetic Code Expansion. United States: N. p., 2018. Web. doi:10.3390/genes9110537.
Hoffman, Kyle, Crnković, Ana, & Söll, Dieter. Versatility of Synthetic tRNAs in Genetic Code Expansion. United States. https://doi.org/10.3390/genes9110537
Hoffman, Kyle, Crnković, Ana, and Söll, Dieter. Wed . "Versatility of Synthetic tRNAs in Genetic Code Expansion". United States. https://doi.org/10.3390/genes9110537. https://www.osti.gov/servlets/purl/1610398.
@article{osti_1610398,
title = {Versatility of Synthetic tRNAs in Genetic Code Expansion},
author = {Hoffman, Kyle and Crnković, Ana and Söll, Dieter},
abstractNote = {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.},
doi = {10.3390/genes9110537},
journal = {Genes},
number = 11,
volume = 9,
place = {United States},
year = {Wed Nov 07 00:00:00 EST 2018},
month = {Wed Nov 07 00:00:00 EST 2018}
}

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