Catalytic RNA Ribozymes

In 1989, Sidney Altman and Thomas Cech were awarded the Nobel Prize in chemistry for a discovery that changed not only the field of biocatalysis, but also our perception of the molecular basis of life on Earth [118]. They showed that RNA, which until then was considered an innocent carrier of hereditary information, can actually catalyze reactions [119,120]. Two different RNA molecules were shown to catalyze site-specificphosphodiesterbondcleavage,withrate enhancements ofseveral orders of magnitude. This discovery of nonprotein biocatalysts came as a complete surprise, and laid open many questions and opportunities [121,122]. 

In a nutshell, RNA transcribes the genetic code of the DNA, and transfers it to the cell s protein factories. This process also requires a shearing and splicing of the RNA molecules, because DNA strands contain regions which are not essential for 

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There are other ways in which nucleic-acid-related compounds could be exploited as therapeutics. A new, emerging area concerns the application of RNA as a dmg. The discovery of catalytic RNA (ribozymes) by Cech and Altman was a fundamental advance in nucleic acid chemistry. According to traditional double helix dogma, RNA was a passive information-transmitting molecule. The identification of ribozymes enabled the conceptual advance that RNA can also act as a catalyst for the following biochemical processes ... 

The chemical nature of enzyme was controversial for a long time, until Buchner succeeded in isolating an enzyme system (zymase) from yeast in a cell-free extract in 1897.2) Urease was then crystallized by Sumner in 1926,3) followed by crystallization of several proteolytic enzymes by Northlop and his colleagues. At present the chemical nature of enzyme is defined as a protein with catalytic activity based on the specific activaiton of its substrate. However, this definition has been somewhat open to debate since a catalytic RNA, ribozyme, was discoved in 1982. 

In this section is an overview of some historical aspects of enzyme studies with special emphasis on new methods of purification, structure determination, and research on the reaction mechanism of an enzyme. Enzyme application for medical and industrial use and development of novel enzymes such as catalytic RNA (ribozyme) and catalytic antibody (abzymes) are also briefly described. 

There was a time when proteins were considered the only biological macromolecules capable of catalysis. The discovery of the catalytic activity of RNA has thus had a profound impact on the way biochemists think. A few enzymes with RNA components had been discovered, such as telomerase (Chapter 10) and RNase P, an enzyme that cleaves extra nucleotides off the 5 ends of tRNA precursors. It was later shown that the RNA portion of RNase P has the catalytic activity. The field of catalytic RNA (ribozymes) was launched in earnest by the discovery of RNA that catalyzes its own selfsplicing. It is easy to see a connection between this process and the splicing... 

Most enzymes are proteins, but some catalytic RNAs (ribozymes) are known. 

Catalytic RNA ( Ribozymes ) and Conjectures about a Prebiotic RNA World ... 

RNAs can be functionally divided into messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), and catalytic RNA (ribozyme). Other functional RNAs include protein-conjugated RNAs, such as small nuclear ribonucleo-proteins (snRNPs). 

In addition to the catalytic action served by the snRNAs in the formation of mRNA, several other enzymatic functions have been attributed to RNA. Ribozymes are RNA molecules with catalytic activity. These generally involve transesterification reactions, and most are concerned with RNA metabofism (spfic-ing and endoribonuclease). Recently, a ribosomal RNA component was noted to hydrolyze an aminoacyl ester and thus to play a central role in peptide bond function (peptidyl transferases see Chapter 38). These observations, made in organelles from plants, yeast, viruses, and higher eukaryotic cells, show that RNA can act as an enzyme. This has revolutionized thinking about enzyme action and the origin of life itself. 

Magnesium has its role intimately intertwined with phosphate in many phosphoryl transfer reactions, as Mg-ATP in muscle contraction, in the stabilization of nucleic acid structures as well as in the catalytic activity of ribozymes (catalytic RNA molecules). It also serves as a structural component of enzymes, and is found as the metal centre in chlorophylls, which absorbs light energy in photosynthesis. 

As stated previously in the introductory section, T. R. Cech and co-workers reported on the first catalytic RNA or ribozyme, the self-splicing intron of the... 

Since the discovery that RNA molecules can possess catalytic activities, ribozymes have become a fascinating field both for academic researchers and the pharmaceutical industry. In this review, we emphasize the latest progress made in structure determination of ribozymes as well as the generation of DNA and RNA enzymes with novel catalytic properties by combinatorial approaches. 

One of the most interesting ribozymes isolated by in vitro selection techniques is a novel catalytic RNA that promoted the formation of a glycosidic bond... 

Pyle AM (1996) Catalytic reaction mechanisms and structural features of group II intron ribozymes, p 75-107. In Eckstein F, Lilley DMJ (ed) Catalytic RNA, vol 10 Springer, Berlin Heidelberg New York... 

Although most catalysts in living systems are enzymes, they are not the only ones. Ribozymes are catalytic RNA molecules. These also play important roles in the metabolism of living organisms, including specifically the synthesis of proteins. 

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