Natural ribozymes

RNA catalysis is not only concerned with RNA cleavage non-natural ribozymes that show ligase activity (Bartel and Szostak, 1993) were obtained and many (so far not yet successful) efforts have been undertaken to prepare a ribozyme with RNA replicase activity. RNA catalysis does not only operate on RNA, nor do nucleic acid catalysts require the ribose backbone. Ribozymes were trained by evolutionary techniques to process DNA rather than their natural RNA substrate (Beaudry and Joyce, 1992), and catalytically active DNA molecules were evolved as well (Breaker and Joyce, 1994 Cuenoud and Szostak, 1995). Systematic studies revealed many other examples of RNA catalysis on non-nucleic acid substrates (see... 

J. A. Doudna and T. R. Cech, The chemical repertoire of natural ribozymes, Nature... 

In addition to natural ribozymes several synthetic ribozymes with new activity have been obtained by in-vitro selection techniques. Starting with a pool of random RNA sequences, molecules with a desired activity can be isolated by successive cycles of activity selection, reverse transcription into DNA, and amplification by polymerase chain reaction [4a,b]. 

The so-called ribozymes (Box 22) were discovered in 1982 by T. Cech and S. Altman. The naturally occurring species catalyze predominantly one reaction type -hydrolysis or transesterification of phosphodiester bonds in RNA. A very important natural ribozyme is the ribosome. On the basis of X-ray crystallographic investigations it was recently shown that the active site for the peptide bond-formation reaction is composed exclusively of RNA. 

Lehmann K, Schmidt U. Group 11 introns structure and catalytic versatility of large natural ribozymes. Crit. Rev. Biochem. Mol. Biol. 2003 38(3) 249-303. 

RNA Catalysis Is Ubiquitous in Biology Reactions Catalyzed by Natural Ribozymes The Potential for Catalysis by Ribozymes... 

The resolution of the 3-D structure of the small and large subunit of ribosomal RNA (rRNA) revealed an intricate, globular secondary structure with extensive basestacking interactions. Forming stems and loops show that rRNA does not serve as a scaffold alone however, in fact, it also creates the framework for the ribosome and the functional sites to act as a true natural ribozyme. The functional sites are located in the center of the ribozyme. It has been said that tRNA looks like Nature s attempt to make RNA do the job of a protein rRNA takes this notion one giant step further to make a functional molecule out of RNA. Beyond this, Nature has to resort to proteins. 

It is intriguing that the aforementioned natural ribozyme, the peptidyltransferase activity of the ribosome is an ancient RNA machine. Many ribosomal proteins are evolutionary conserved and contain multiple examples of glycine-, lysine-, and arginine-rich protein extensions that penetrate deep into the ribosomal RNA. Random condensation from amino acids likely produced these basic peptides. 

Using the methods of in vitro selection and in vitro evolution not only the functionahty and specificity of natural ribozymes could be altered or improved, but also nucleic acid based catalysts with new catalytic activities could be evolved. The latest results in this field demonstrate that ribozymes or deoxyri-... 

While enzymological research over several decades has provided a rather detailed understanding of how certain enzymes accelerate chemical reactions, knowledge about ribozyme mechanisms and catalytic strategies is scarce in comparison. For some natural ribozymes, mechanistic and structural studies were carried out, but artificial ribozymes remain largely uncharacterized. Therefore it is unclear in many cases whether these catalysts are passive containers working solely by substrate pre-organization, or whether there are specific effects on the activation parameters of the reaction. 

The field of natural ribozymes has been extensively reviewed. ... 

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