Biopolym. Cell. 1995; 11(1):20-29.
Properties of ribozyme from Tetrahymena thermophila
1Fedorenko E. S., 1Irodov D. M., 1Kordium V. A.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    Kiev, Ukraine

Abstract

Ribozymes are RNA molecules that contain a catalytic core and promote cleavage and ligation substrat RNA. Ribozymes can attain levels of rate enhancement and specificity similar to those of protein enzymes. Some protein enzymes use cofactors including metal ions to facilitate chemical reactions. Ribozymes generally require divalent cations for their activity.
The discovery of catalytic RNA has created interest in using RNA enzymes, or «ribozymes», to target the degradation of specific RNA molecules in vivo. Targeted destruction of viral or cellular mRNA, to eliminate the formation of a protein that is deleterious in a disease state, has potential therapeutic utility. Targeting also has potential utility for identification of gene fanction, analogous to experiments using anlisense oligonucleotides. The first ribozyme identified was tile self-splising intron of the large subunit ribosomal RNA of the ciliated protozoan, Tetrahymena termophila. This RNA is a member of a phylogenetically diverse family of introns called group I, which now consists of more than 100 sequenced examples.
The purpose of this review is to integrate a great number data available now about Tetrahymena ribozyme.

References

[1] Cech TR. Ribozymes and their medical implications. JAMA. 1988;260(20):3030-4.
[2] Haseloff J, Gerlach WL. Simple RNA enzymes with new and highly specific endoribonuclease activities. Nature. 1988;334(6183):585-91.
[3] Rossi JJ, Sarver N. RNA enzymes (ribozymes) as antiviral therapeutic agents. Trends Biotechnol. 1990;8(7):179-83.
[4] Colman A. Antisense strategies in cell and developmental biology. J Cell Sci. 1990;97 ( Pt 3):399-409.
[5] Kruger K, Grabowski PJ, Zaug AJ, Sands J, Gottschling DE, Cech TR. Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell. 1982;31(1):147-57.
[6] Been MD, Perrotta AT. Group I intron self-splicing with adenosine: evidence for a single nucleoside-binding site. Science. 1991;252(5004):434-7.
[7] Zaug AJ, Cech TR. The intervening sequence RNA of Tetrahymena is an enzyme. Science. 1986;231(4737):470-5.
[8] Inoue T, Sullivan FX, Cech TR. New reactions of the ribosomal RNA precursor of Tetrahymena and the mechanism of self-splicing. J Mol Biol. 1986;189(1):143-65.
[9] Davies RW, Waring RB, Ray JA, Brown TA, Scazzocchio C. Making ends meet: a model for RNA splicing in fungal mitochondria. Nature. 1982;300(5894):719-24.
[10] Burke JM. Molecular genetics of group I introns: RNA structures and protein factors required for splicing--a review. Gene. 1988;73(2):273-94.
[11] Cech TR. Conserved sequences and structures of group I introns: building an active site for RNA catalysis--a review. Gene. 1988;73(2):259-71.
[12] Latham JA, Cech TR. Defining the inside and outside of a catalytic RNA molecule. Science. 1989;245(4915):276-82.
[13] Young B, Herschlag D, Cech TR. Mutations in a nonconserved sequence of the Tetrahymena ribozyme increase activity and specificity. Cell. 1991;67(5):1007-19.
[14] Michel F, Hanna M, Green R, Bartel DP, Szostak JW. The guanosine binding site of the Tetrahymena ribozyme. Nature. 1989;342(6248):391-5.
[15] Yarus M, Illangesekare M, Christian E. An axial binding site in the Tetrahymena precursor RNA. J Mol Biol. 1991;222(4):995-1012.
[16] Yarus M, Majerfeld I. Co-optimization of ribozyme substrate stacking and L-arginine binding. J Mol Biol. 1992;225(4):945-9.
[17] Herschlag D, Cech TR. Catalysis of RNA cleavage by the Tetrahymena thermophila ribozyme. 2. Kinetic description of the reaction of an RNA substrate that forms a mismatch at the active site. Biochemistry. 1990;29(44):10172-80.
[18] Been MD, Cech TR. One binding site determines sequence specificity of Tetrahymena pre-rRNA self-splicing, trans-splicing, and RNA enzyme activity. Cell. 1986;47(2):207-16.
[19] Zaug AJ, Been MD, Cech TR. The Tetrahymena ribozyme acts like an RNA restriction endonuclease. Nature. 1986 Dec 4-10;324(6096):429-33.
[20] Doudna JA, Szostak JW. RNA-catalysed synthesis of complementary-strand RNA. Nature. 1989;339(6225):519-22.
[21] Robertson DL, Joyce GF. Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA. Nature. 1990;344(6265):467-8.
[22] Beaudry AA, Joyce GF. Minimum secondary structure requirements for catalytic activity of a self-splicing group I intron. Biochemistry. 1990;29(27):6534-9.
[23] Doudna JA, Cormack BP, Szostak JW. RNA structure, not sequence, determines the 5' splice-site specificity of a group I intron. Proc Natl Acad Sci U S A. 1989;86(19):7402-6.
[24] Doudna JA, Gerber AS, Cherry JM, Szostak JW. Genetic dissection of an RNA enzyme. Cold Spring Harb Symp Quant Biol. 1987;52:173-80.
[25] Zaug AJ, Grabowski PJ, Cech TR. Autocatalytic cyclization of an excised intervening sequence RNA is a cleavage-ligation reaction. Nature. 1983 Feb 17-23;301(5901):578-83.
[26] Been MD, Cech TR. Selection of circularization sites in a group I IVS RNA requires multiple alignments of an internal template-like sequence. Cell. 1987;50(6):951-61.
[27] Inoue T, Sullivan FX, Cech TR. New reactions of the ribosomal RNA precursor of Tetrahymena and the mechanism of self-splicing. J Mol Biol. 1986;189(1):143-65.
[28] Zaug AJ, Kent JR, Cech TR. A labile phosphodiester bond at the ligation junction in a circular intervening sequence RNA. Science. 1984;224(4649):574-8.
[29] Zaug AJ, Kent JR, Cech TR. Reactions of the intervening sequence of the Tetrahymena ribosomal ribonucleic acid precursor: pH dependence of cyclization and site-specific hydrolysis. Biochemistry. 1985;24(22):6211-8.
[30] Piccirilli JA, McConnell TS, Zaug AJ, Noller HF, Cech TR. Aminoacyl esterase activity of the Tetrahymena ribozyme. Science. 1992;256(5062):1420-4.
[31] Herschlag D. Implications of ribozyme kinetics for targeting the cleavage of specific RNA molecules in vivo: more isn't always better. Proc Natl Acad Sci U S A. 1991;88(16):6921-5.
[32] Beaudry AA, Joyce GF. Directed evolution of an RNA enzyme. Science. 1992;257(5070):635-41.
[33] Murphy FL, Cech TR. Alteration of substrate specificity for the endoribonucleolytic cleavage of RNA by the Tetrahymena ribozyme. Proc Natl Acad Sci U S A. 1989;86(23):9218-22.
[34] Celander DW, Cech TR. Visualizing the higher order folding of a catalytic RNA molecule. Science. 1991;251(4992):401-7.