The Caenorhabditis elegans Homologue of Thioredoxin Reductase Contains a Selenocysteine Insertion Sequence (SECIS) Element That Differs from Mammalian SECIS Elements but Directs Selenocysteine Incorporation

Christoph Buettner,John W Harney,Marla J Berry

doi:10.1074/jbc.274.31.21598

Christoph Buettner, John W Harney + Show 1 more

Open Access

https://doi.org/10.1074/jbc.274.31.21598

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Abstract

Thioredoxin reductases (TRR) serve critical roles in maintaining cellular redox states. Two isoforms of TRR have been identified in mammals: both contain a penultimate selenocysteine residue that is essential for catalytic activity. A search of the genome of the invertebrate, Caenorhabditis elegans, reveals a gene highly homologous to mammalian TRR, with a TGA selenocysteine codon at the corresponding position. A selenocysteyl-tRNA was identified in this organism several years ago, but no selenoproteins have been identified experimentally. Herein we report the first identification of a C. elegans selenoprotein. By (75)Se labeling of C. elegans, one major band was identified, which migrated with the predicted mobility of the C. elegans TRR homologue. Western analysis with an antibody against human TRR provides strong evidence for identification of the C. elegans selenoprotein as a member of the TRR family. The 3'-untranslated region of this gene contains a selenocysteine insertion sequence (SECIS) element that deviates at one position from the previously invariant consensus "AUGA." Nonetheless, this element functions to direct selenocysteine incorporation in mammalian cells, suggesting conservation of the factors recognizing SECIS elements from worm to man.

Highlights

The synthesis of selenoproteins requires several specialized components of the translational machinery
Identification of Selenoproteins in C. elegans—To identify selenoproteins in C. elegans, we developed a 75Se labeling technique based on their food source, bacteria
We report identification of the first selenoprotein and the first selenocysteine insertion sequence (SECIS) element in C. elegans

Summary

Introduction

The synthesis of selenoproteins requires several specialized components of the translational machinery (reviewed in Ref. 1). This protein migrates with the predicted size of a thioredoxin reductase homologue in the C. elegans sequence data base. TRR Is the Only Eukaryotic Selenoprotein Homologue in C. elegans with a UGA Selenocysteine Codon—We performed a search of the C. elegans genome data base with the sequences of all known mammalian selenoproteins.

Results

Conclusion