Article
- The EMBO Journal (2005) 24, 1596 - 1607
- doi:10.1038/sj.emboj.7600642
Published online: 24 March 2005
Recoding elements located adjacent to a subset of eukaryal selenocysteine-specifying UGA codons
Michael T Howard1, Gaurav Aggarwal1, Christine B Anderson1, Shikha Khatri1,a, Kevin M Flanigan1,2 and John F Atkins1,3
- Department of Human Genetics, University of Utah, Salt Lake City, UT, USA
- Departments of Neurology and Pathology, University of Utah, Salt Lake City, UT, USA
- Bioscience Institute, University College Cork, Cork, Ireland
Correspondence to:
Michael T Howard, Department of Human Genetics, University of Utah, 15 N 2030 E, Rm 2100, Salt Lake City, UT 84112, USA. Tel.: +1 801 585 1927; Fax: +1 801 585 3910; E-mail: mhoward@genetics.utah.edu
aPresent address: Genome Research Institute, University of Cincinnati, Bldg D Room 227, 2180 E Galbraith Road, Cincinnati, OH 45237, USA
Received 25 January 2005; Accepted 7 March 2005
Abstract
Incorporation of the 21st amino acid, selenocysteine, into proteins is specified in all three domains of life by dynamic translational redefinition of UGA codons. In eukarya and archaea, selenocysteine insertion requires a cis-acting selenocysteine insertion sequence (SECIS) usually located in the 3'UTR of selenoprotein mRNAs. Here we present comparative sequence analysis and experimental data supporting the presence of a second stop codon redefinition element located adjacent to a selenocysteine-encoding UGA codon in the eukaryal gene, SEPN1. This element is sufficient to stimulate high-level (6%) translational redefinition of the SEPN1 UGA codon in human cells. Readthrough levels further increased to 12% when tested in the presence of the SEPN1 3'UTR SECIS. Directed mutagenesis and phylogeny of the sequence context strongly supports the importance of a stem loop starting six nucleotides 3' of the UGA codon. Sequences capable of forming strong RNA structures were also identified 3' adjacent to, or near, selenocysteine-encoding UGA codons in the Sps2, SelH, SelO, and SelT selenoprotein genes.
Keywords:
- readthrough,
- redefinition,
- selenocysteine,
- selenoprotein,
- termination
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