title: SECIS elements in the coding regions of selenoprotein transcripts are functional in higher eukaryotes.
abstract: Expression of selenocysteine (Sec)-containing proteins requires the presence of a cis-acting mRNA structure, called selenocysteine insertion sequence (SECIS) element. In bacteria, this structure is located in the coding region immediately downstream of the Sec-encoding UGA codon, whereas in eukaryotes a completely different SECIS element has evolved in the 3'-untranslated region. Here, we report that SECIS elements in the coding regions of selenoprotein mRNAs support Sec insertion in higher eukaryotes. Comprehensive computational analysis of all available viral genomes revealed a SECIS element within the ORF of a naturally occurring selenoprotein homolog of glutathione peroxidase 4 in fowlpox virus. The fowlpox SECIS element supported Sec insertion when expressed in mammalian cells as part of the coding region of viral or mammalian selenoproteins. In addition, readthrough at UGA was observed when the viral SECIS element was located upstream of the Sec codon. We also demonstrate successful de novo design of a functional SECIS element in the coding region of a mammalian selenoprotein. Our data provide evidence that the location of the SECIS element in the untranslated region is not a functional necessity but rather is an evolutionary adaptation to enable a more efficient synthesis of selenoproteins.
authors.affiliation: Department of Biochemistry, University of Nebraska Beadle Center, Lincoln, NE 68588, USA.
authors.forename: Heiko
authors.initials: H
authors.lastname: Mix
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Lobanov
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D019295:Computational Biology; D005587:Fowlpox virus / Q000201:enzymology / Q000235:genetics; D015894:Genome, Human; D016679:Genome, Viral; D023281:Genomics; D005979:Glutathione Peroxidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D012333:RNA, Messenger / Q000737:chemistry*; D038621:Regulatory Sequences, Ribonucleic Acid; D051140:Selenoproteins / Q000096:biosynthesis / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D012333:RNA, Messenger; D038621:Regulatory Sequences, Ribonucleic Acid; D051140:Selenoproteins; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase