Distinct genetic code expansion strategies for selenocysteine and pyrrolysine are reflected in different aminoacyl-tRNA formation systems

Yuan, Jing; O’Donoghue, Patrick; Ambrogelly, Alex; Gundllapalli, Sarath; Sherrer, R. Lynn; Palioura, Sotiria; Simonović, Miljan; Söll, Dieter

doi:10.1016/j.febslet.2009.11.005

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Volume 584, Issue 2 , Pages 342-349, 21 January 2010

Distinct genetic code expansion strategies for selenocysteine and pyrrolysine are reflected in different aminoacyl-tRNA formation systems

Edited by Michael Ibba

Jing Yuan
- Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA
- Both authors contributed equally.
- Corresponding authors.
Patrick O’Donoghue
- Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA
- Both authors contributed equally.
- Corresponding authors.
Alex Ambrogelly
- Schering-Plough Corporation, Kenilworth, NJ 07033-0530, USA
Sarath Gundllapalli
- Schering-Plough Corporation, Kenilworth, NJ 07033-0530, USA
R. Lynn Sherrer
- Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA
Sotiria Palioura
- Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA
Miljan Simonović
- Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA
Dieter Söll
- Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA
- Department of Chemistry, Yale University, New Haven, CT 06520-8114, USA

Received 21 October 2009; received in revised form 3 November 2009; accepted 4 November 2009. published online 09 November 2009.

Abstract

Selenocysteine and pyrrolysine, known as the 21st and 22nd amino acids, are directly inserted into growing polypeptides during translation. Selenocysteine is synthesized via a tRNA-dependent pathway and decodes UGA (opal) codons. The incorporation of selenocysteine requires the concerted action of specific RNA and protein elements. In contrast, pyrrolysine is ligated directly to tRNA^Pyl and inserted into proteins in response to UAG (amber) codons without the need for complex re-coding machinery. Here we review the latest updates on the structure and mechanisms of molecules involved in Sec-tRNA^Sec and Pyl-tRNA^Pyl formation as well as the distribution of the Pyl-decoding trait.

Keywords: o-phosphoseryl-tRNA^Sec kinase, Sep-tRNA:Sec-tRNA synthase, Pyrrolysyl-tRNA synthetase, Stop codon re-coding, Natural suppression