AI Article Synopsis

  • The 21st amino acid, selenocysteine, is incorporated into proteins by redefining UGA codons in all three domains of life.
  • In eukaryotes and archaea, this process involves a selenocysteine insertion sequence (SECIS) typically found in the 3'UTR of selenoprotein mRNAs.
  • Research indicates a second redefinition element near the UGA codon in the SEPN1 gene that boosts the translational redefinition rate, particularly when combined with the SECIS, emphasizing the role of specific RNA structures in enhancing this process.

Article 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1142574PMC
http://dx.doi.org/10.1038/sj.emboj.7600642DOI Listing

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