Tetrahymena, self-splicing

First, given the wide range of prebiotic nucleic acids, ribose-based polymers may be the most eminently suited for catalysis. Eschenmoser has pointed out, for example, that nucleic acids constructed from hexose nucleotides form inflexible ribbon structures,61 poorly suited for convoluting into the complex shapes that are required for catalysis (e.g., the backbone of the projected tertiary structure of the Tetrahymena self-splicing intron folds back on itself a number of times).62 Conversely, backbones composed of acyclic nucleotides may be too flexible to adopt stable secondary structures (since a great deal of entropy would necessarily be lost on freezing into a given conformer). Ribose, on the other hand, has a limited flexibility because of its pseudorotation cycle, and RNA can adopt a variety of helical conformations. 

Unlike the Tetrahymena self-splicing intron, RNase P is believed to recognize its substrates via highly conserved structural motifs. With pre-tRNA molecules, the primary site of interaction is believed to be the 3 terminal (but not internal)... 

Based on the observation of self splicing by the 23S RNA of Tetrahymena, it is assumed that the cleavage and rejoining of the phosphodiester bond is catalyzed by the RNA components of the spliceosome. The proteins of the spliceosome are believed to be important for the recognition of the 5 and 3 splice sites and for the formation of a defined structure in the spliceosome. Thus, the proteins of the spliceosome play a decisive role in the choice of the splice site and the effeciency of splicing. 

The RNA world hypothesis requires a nucleotide polymer to reproduce itself. Can a ribozyme bring about its own synthesis in a template-directed manner The self-splicing rRNA intron of Tetrahymena (Fig. 26-26) catalyzes the reversible attack of a guanosine residue on the 5 splice junction (Fig. 26-37). If the 5 splice site and the internal guide sequence are removed from the intron, the rest of the intron can bind RNA strands paired with short oligonucleotides. Part of the remaining intact intron effectively acts as a template for the... 

Self-splicing KNA. The precursor to the 26S rRNA of Tetrahymena contains a 413-nucleotide intron, which was shown by Cedi and coworkers to be selfsplicing, i.e., not to require a protein catalyst for maturation.581 582 This pre-rRNA is a ribozyme with true catalytic properties (Chapter 12). It folds into a complex three-dimensional structure which provides a binding site for free guanosine whose 3-OH attacks the phosphorus at the 5 end of the intron as shown in Fig. 28-18A, step a. The reaction is a simple displacement on phosphorus, a transesterification similar to that in the first step of pancreatic ribonuclease action (Eq. 12-25). The resulting free 3-OH then attacks the phosphorus atom at the other end of the intron (step b) to accomplish the splicing and to release the intron as a linear polynucleotide. The excised intron undergoes... 

Self-splicing of pre-rRNA from the protozoan Tetrahymena. The first step is a transesterification reaction in which the 3 hydroxyl group of a guanosine attacks the phosphodiester bond at the 5 splice site. The second step involves another transesterification reaction in which the 3 hydroxyl group of the upstream exon attacks the phosphodiester bond at the 3 splice site and displaces the 3 hydroxyl group of the intron. 

Kruger, K., Grabowski, P.J., Zaug, A.J., Sands, J., Gottschling, D.E. and Cech, T.R. (1982) Self-splicing RNA autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell, 31,147-157. 

T. R. Cech, Self-splicing RNA autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena, Cell 1982, 31, 147-157. 

Lehnert, V., Jaeger, L., Michele, F., and Westhof, E. (1996). New loop-loop tertiary interactions in self-splicing introns of subgroup IC and ID A complete 3D model of the Tetrahymena thermophila ribozyme. Chem. Biol. 3, 993—1009. 

Emerick, V. L., and Woodson, S. A. (1993). Self-splicing of the Tetrahymena pre-rRNA is decreased by misfolding during transcription. Biochemistry 32, 14062—14067. 

Karbstein, K., Lee, J., and Herschlag, D. (2007). Probing the role of a secondary structure element at the 5 - and splice sites in group I intron self-splicing The Tetrahymena L-16ScaI ribozyme reveals a new role for the G U pair in self-splicing. Biochemistry 46, 4861-4875. 

In Tetrahymena, the pre-rRNA molecule contains an intron that is removed by self-splicing (in the presence of guanosine, GMP, GDP or GTP) without the need for involvement of any protein. This was the first ribozyme discovered but many have since been reported. 

K. Kruger, P.J. Grabowski, A.J. Zaug, J. Sands, D.E. Gottschling, T.R. Chech, Self-Splicing RNA Autoexcision and Autocyclization of the Ribosomal RNA Intervening Sequence of Tetrahymena , Cell, 31, 147 (1982)... 

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