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RNA. May 1999; 5(5): 625–635.
PMCID: PMC1369790

Two distinct SECIS structures capable of directing selenocysteine incorporation in eukaryotes.


Translation of UGA as selenocysteine requires specific RNA secondary structures in the mRNAs of selenoproteins. These elements differ in sequence, structure, and location in the mRNA, that is, coding versus 3' untranslated region, in prokaryotes, eukaryotes, and archaea. Analyses of eukaryotic selenocysteine insertion sequence (SECIS) elements via computer folding programs, mutagenesis studies, and chemical and enzymatic probing has led to the derivation of a predicted consensus structural model for these elements. This model consists of a stem-loop or hairpin, with conserved nucleotides in the loop and in a non-Watson-Crick motif at the base of the stem. However, the sequences of a number of SECIS elements predict that they would diverge from the consensus structure in the loop region. Using site-directed mutagenesis to introduce mutations predicted to either disrupt or restore structure, or to manipulate loop size or stem length, we show that eukaryotic SECIS elements fall into two distinct classes, termed forms 1 and 2. Form 2 elements have additional secondary structures not present in form 1 elements. By either insertion or deletion of the sequences and structures distinguishing the two classes of elements while maintaining appropriate loop size, conversion of a form 1 element to a functional form 2-like element and of a form 2 to a functional form 1-like element was achieved. These results suggest commonality of function of the two classes. The information obtained regarding the existence of two classes of SECIS elements and the tolerances for manipulations of stem length and loop size should facilitate designing RNA molecules for obtaining high-resolution structural information about these elements.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Berry MJ, Banu L, Chen YY, Mandel SJ, Kieffer JD, Harney JW, Larsen PR. Recognition of UGA as a selenocysteine codon in type I deiodinase requires sequences in the 3' untranslated region. Nature. 1991 Sep 19;353(6341):273–276. [PubMed]
  • Berry MJ, Banu L, Harney JW, Larsen PR. Functional characterization of the eukaryotic SECIS elements which direct selenocysteine insertion at UGA codons. EMBO J. 1993 Aug;12(8):3315–3322. [PMC free article] [PubMed]
  • Berry MJ, Kieffer JD, Harney JW, Larsen PR. Selenocysteine confers the biochemical properties characteristic of the type I iodothyronine deiodinase. J Biol Chem. 1991 Aug 5;266(22):14155–14158. [PubMed]
  • Gossen M, Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5547–5551. [PMC free article] [PubMed]
  • Hubert N, Walczak R, Carbon P, Krol A. A protein binds the selenocysteine insertion element in the 3'-UTR of mammalian selenoprotein mRNAs. Nucleic Acids Res. 1996 Feb 1;24(3):464–469. [PMC free article] [PubMed]
  • Kollmus H, Flohé L, McCarthy JE. Analysis of eukaryotic mRNA structures directing cotranslational incorporation of selenocysteine. Nucleic Acids Res. 1996 Apr 1;24(7):1195–1201. [PMC free article] [PubMed]
  • Lesoon A, Mehta A, Singh R, Chisolm GM, Driscoll DM. An RNA-binding protein recognizes a mammalian selenocysteine insertion sequence element required for cotranslational incorporation of selenocysteine. Mol Cell Biol. 1997 Apr;17(4):1977–1985. [PMC free article] [PubMed]
  • Low SC, Berry MJ. Knowing when not to stop: selenocysteine incorporation in eukaryotes. Trends Biochem Sci. 1996 Jun;21(6):203–208. [PubMed]
  • Martin GW, 3rd, Harney JW, Berry MJ. Selenocysteine incorporation in eukaryotes: insights into mechanism and efficiency from sequence, structure, and spacing proximity studies of the type 1 deiodinase SECIS element. RNA. 1996 Feb;2(2):171–182. [PMC free article] [PubMed]
  • Martin GW, 3rd, Harney JW, Berry MJ. Functionality of mutations at conserved nucleotides in eukaryotic SECIS elements is determined by the identity of a single nonconserved nucleotide. RNA. 1998 Jan;4(1):65–73. [PMC free article] [PubMed]
  • Shen Q, Leonard JL, Newburger PE. Structure and function of the selenium translation element in the 3'-untranslated region of human cellular glutathione peroxidase mRNA. RNA. 1995 Jul;1(5):519–525. [PMC free article] [PubMed]
  • Shen Q, McQuilkin PA, Newburger PE. RNA-binding proteins that specifically recognize the selenocysteine insertion sequence of human cellular glutathione peroxidase mRNA. J Biol Chem. 1995 Dec 22;270(51):30448–30452. [PubMed]
  • Shen Q, Wu R, Leonard JL, Newburger PE. Identification and molecular cloning of a human selenocysteine insertion sequence-binding protein. A bifunctional role for DNA-binding protein B. J Biol Chem. 1998 Mar 6;273(10):5443–5446. [PubMed]
  • Turner DH, Sugimoto N, Freier SM. RNA structure prediction. Annu Rev Biophys Biophys Chem. 1988;17:167–192. [PubMed]
  • Walczak R, Carbon P, Krol A. An essential non-Watson-Crick base pair motif in 3'UTR to mediate selenoprotein translation. RNA. 1998 Jan;4(1):74–84. [PMC free article] [PubMed]
  • Walczak R, Westhof E, Carbon P, Krol A. A novel RNA structural motif in the selenocysteine insertion element of eukaryotic selenoprotein mRNAs. RNA. 1996 Apr;2(4):367–379. [PMC free article] [PubMed]

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