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Science 25 March 2005:
Vol. 307. no. 5717, pp. 1969 - 1972
DOI: 10.1126/science.1108329
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Reports

RNA-Dependent Cysteine Biosynthesis in Archaea

Anselm Sauerwald,1 Wenhong Zhu,3 Tiffany A. Major,4 Hervé Roy,5 Sotiria Palioura,1 Dieter Jahn,6 William B. Whitman,4 John R. Yates, 3rd,3 Michael Ibba,5 Dieter Söll1,2*

Several methanogenic archaea lack cysteinyl–transfer RNA (tRNA) synthetase (CysRS), the essential enzyme that provides Cys-tRNACys for translation in most organisms. Partial purification of the corresponding activity from Methanocaldococcus jannaschii indicated that tRNACys becomes acylated with O-phosphoserine (Sep) but not with cysteine. Further analyses identified a class II–type O-phosphoseryl-tRNA synthetase (SepRS) and Sep-tRNA:Cys-tRNA synthase (SepCysS). SepRS specifically forms Sep-tRNACys, which is then converted to Cys-tRNACys by SepCysS. Comparative genomic analyses suggest that this pathway, encoded in all organisms lacking CysRS, can also act as the sole route for cysteine biosynthesis. This was proven for Methanococcus maripaludis, where deletion of the SepRS-encoding gene resulted in cysteine auxotrophy. As the conversions of Sep-tRNA to Cys-tRNA or to selenocysteinyl-tRNA are chemically analogous, the catalytic activity of SepCysS provides a means by which both cysteine and selenocysteine may have originally been added to the genetic code.

1 Department of Molecular Biophysics and Biochemistry
2 Department of Chemistry, Yale University, New Haven, CT 06520–8114, USA.
3 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
4 Department of Microbiology, University of Georgia, Athens, GA 30602–2605, USA.
5 Department of Microbiology, The Ohio State University, Columbus, OH 43210–1292, USA.
6 Department of Microbiology, Technische Universität Braunschweig, D-38106 Braunschweig, Germany.

Note added in proof: A recently published bioinformatics analysis has suggested that Mj1660 is a class II CysRS (32).

* To whom correspondence should be addressed. E-mail: soll{at}trna.chem.yale.edu

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