A ribozyme (from ribonucleic acid enzyme, also called RNA enzyme or catalytic RNA) is an RNA molecule that catalyzes a chemical reaction. Many natural ribozymes catalyze either the hydrolysis of one of their own phosphodiester bonds, or the hydrolysis of bonds in other RNAs, but they have also been found to catalyze the aminotransferase activity of the ribosome. Ribozyme is a Norwegian hard rock band formed in 1998. ... For other uses, see RNA (disambiguation). ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... For other uses, see RNA (disambiguation). ... 3D (left and center) and 2D (right) representations of the terpenoid molecule atisane. ... For other uses, see Chemical reaction (disambiguation). ... Hydrolysis is a chemical reaction or process in which a chemical compound is broken down by reaction with water. ... Diagram of phosphodiester bonds between nucleotides A phosphodiester bond is a group of strong covalent bonds between the phosphorus atom in a phosphate group and two other molecules over two ester bonds. ... In biochemistry, a transaminase or an aminotransferase is an enzyme that catalyzes a type of reaction between an amino acid and an α-keto acid. ... Figure 1: Ribosome structure indicating small subunit (A) and large subunit (B). ...

Investigators studying the origin of life have produced ribozymes in the laboratory that are capable of catalyzing their own synthesis under very specific conditions, such as an RNA polymerase ribozyme.^[1] Mutagenesis and selection has been performed resulting in isolation of improved variants of the "Round-18" polymerase ribozyme from 2001. "B6.61" is able to add up to 20 nucleotides to a primer template in 24 hours, until it decomposes by hydrolysis of its phosphodiester bonds.^[2] For the definition, see Life. ... A single chemical reaction is said to have undergone autocatalysis, or be autocatalytic, if the reaction product is itself the catalyst for that reaction. ... This article does not cite any references or sources. ... A nucleotide is an organic molecule consisting of a heterocyclic nucleobase (a purine or a pyrimidine), a pentose sugar (deoxyribose in DNA or ribose in RNA), and a phosphate or polyphosphate group. ...

Some ribozymes may play an important role as therapeutic agents, as enzymes which tailor defined RNA sequences, as biosensors, and for applications in functional genomics and gene discovery.^[3] A biosensor is a device for the detection of an analyte that combines a biological component with a physicochemical detector component. ... A DNA microarray Functional genomics is a field of molecular biology that attempts to make use of the vast wealth of data produced by genomic projects (such as genome sequencing projects) to describe gene (and protein!) functions and interactions. ...

Discovery

Schematic showing ribozyme cleavage of RNA.

Before the discovery of ribozymes, enzymes, which are defined as catalytic proteins,^[4] were the only known biological catalysts. In 1967, Carl Woese, Francis Crick, and Leslie Orgel were the first to suggest that RNA could act as a catalyst based upon findings that it can form complex secondary structures.^[5] The first ribozymes were discovered in the 1980s by Thomas R. Cech, who was studying RNA splicing in the ciliated protozoan Tetrahymena thermophila and Sidney Altman, who was working on the bacterial RNase P complex. The ribozymes were found in the intron of an RNA transcript, which removed itself from the transcript and in the RNA component of the RNase P complex, which is involved in the maturation of pre-tRNAs. In 1989, Thomas R. Cech and Sidney Altman won the Nobel Prize in chemistry for their "discovery of catalytic properties of RNA."^[6] The term ribozyme was first introduced by Kelly Kruger et al. in 1982 in a paper published in Cell. Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... A representation of the 3D structure of myoglobin showing coloured alpha helices. ... Catalyst redirects here. ... Year 1967 (MCMLXVII) was a common year starting on Sunday (link will display full calendar) of the 1967 Gregorian calendar. ... Carl Richard Woese (born July 15, 1928, Syracuse, New York) is an American microbiologist famous for defining the Archaea (a new domain or kingdom of life) in 1977 by phylogenetic taxonomy of 16S ribosomal RNA, a technique pioneered by Woese and which is now standard practice. ... Francis Harry Compton Crick OM FRS (8 June 1916 – 28 July 2004), (Ph. ... Leslie Eleazer Orgel (born Jan 12, 1927 in London) is a chemist. ... A representation of the 3D structure of the myoglobin protein. ... Year 1980 (MCMLXXX) was a leap year starting on Tuesday (link displays the 1980 Gregorian calendar). ... Thomas R. Cech received Nobel Prize in 1989 because he discovered the catalytic properties of RNA with Sidney Altman. ... In genetics, splicing is a modification of genetic information after transcription, in which introns of precursor messenger RNA (pre-mRNA) are removed and exons of it are joined. ... cross-section of two cilia, showing 9+2 structure A cilium (plural cilia) is a fine projection from a eukaryotic cell that constantly beats in one direction. ... Protozoa (in Greek protos = first and zoon = animal) are single-celled creatures with nuclei that show some characteristics usually associated with animals, most notably mobility and heterotrophy. ... Species T hegewischi Tetrahymena are ciliate protozoa, common in aquatic habitats. ... Sidney Altman Sidney Altman (born May 7, 1939) is a Canadian-born molecular biologist, who is currently the Sterling Professor of Molecular, Cellular, and Developmental Biology and Chemistry at Yale University. ... Crystal structure of RNase P with substrate tRNA (green), PDB 2A64 Ribonuclease P (RNase P) is a type of Ribonuclease and is currently under heavy research. ... Diagram of the location of introns and exons within a gene. ... Transfer RNA (abbreviated tRNA) is a small RNA chain (74-93 nucleotides) that transfers a specific amino acid to a growing polypeptide chain at the ribosomal site of protein synthesis during translation. ... Thomas R. Cech received Nobel Prize in 1989 because he discovered the catalytic properties of RNA with Sidney Altman. ... Sidney Altman Sidney Altman (born May 7, 1939) is a Canadian-born molecular biologist, who is currently the Sterling Professor of Molecular, Cellular, and Developmental Biology and Chemistry at Yale University. ... The Nobel Prize (Swedish: ) was established in Alfred Nobels will in 1895, and it was first awarded in Physics, Chemistry, Physiology or Medicine, Literature, and Peace in 1901. ... For other uses, see Chemistry (disambiguation). ... Cell is a bi-monthly peer-reviewed scientific journal which publishes novel research in any area of experimental biology that is significant outside its field. ...

It had been a firmly established belief in biology that catalysis is reserved for proteins. However in 1989 the Nobel Prize was presented to Sidney Altman and Tomas Cech for discovering that RNA can catalyze a reaction. In retrospect, catalytic RNA makes a lot of sense. This is based on the old question regarding the origin of life: Which comes first, enzymes that do the work of the cell or nucleic acids that carry the information required to produce the enzymes? Nucleic acids as catalysts circumvents this problem.^[7]

Research leading to the discovery that RNA can act as a catalyst started in the 1970’s. Thomas Cech, at the University of Colorado at Boulder, was studying the excision of introns in a ribosomal RNA gene in Tetrahymena thermophila. In attempting to purify the enzyme responsible for splicing reaction, he instead found , much of his amazement , that intron could be spliced out in the absence of any added cell extract. Much as they tried, Cech and his colleagues could not identify any protein associated with the splicing reaction. After much work, Cech proposed that the intron sequence portion of the RNA had properties of an enzyme enabling it to break and reform phosphodiester bonds. At about the same time, Sidney Altman, who is a Professor at Yale University, was studying the way tRNA molecules are processed in the cell when he and his colleagues isolated a enzymes called RNase-P, which is responsible for conversion of a precursor tRNA into the active tRNA. Much of their surprise, they found that RNase-P contained RNA in addition to protein and that RNA was an essential component of the active enzyme. This was such a foreign idea that they had difficulty publishing their findings. The following year, Altman demonstrated the final bit of evidence establishing that RNA can act as a catalyst by showing that the RNase-P RNA submit could catalyze the cleavage of precursor tRNA into active tRNA in the absence of the protein component. The University of Colorado at Boulder (CU-Boulder, UCB officially[3]; Colorado and CU colloquially) is the flagship university of the University of Colorado System in Boulder, Colorado. ... Yale redirects here. ... Transfer RNA (abbreviated tRNA) is a small RNA chain (74-93 nucleotides) that transfers a specific amino acid to a growing polypeptide chain at the ribosomal site of protein synthesis during translation. ...

Since Cech’s and Altman’s discovery, other investigators have discovered other example of self-cleaving RNA sot catalytic RNA molecules dubbed ribozymes have either a hairpin – or hammerhead – shaped active center and a unique secondary structure allowing them to cleave other RNA molecules at specific sequences. It is possible to produce in the laboratory ribozymes that will specifically cleave my RNA molecule. These RNA catalysts may have pharmaceuticals applications. For example , a ribozyme has been designed to cleave the RNA of HIV. By placing a ribozyme in the cell all incoming virus particles that express this particular gene will have the RNA product cleaved by the ribozyme, which ,in the end would kill all invading virus particles.

Activity

Although most ribozymes are quite rare in the cell, their roles are sometimes essential to life. For example, the functional part of the ribosome, the molecular machine that translates RNA into proteins, is fundamentally a ribozyme. Ribozymes often have divalent metal ions such as Mg²⁺ as cofactors. This article is about life in general. ... Figure 1: Ribosome structure indicating small subunit (A) and large subunit (B). ... ... Translation is the second stage of protein biosynthesis (part of the overall process of gene expression). ... A cofactor is any substance that needs to be present in addition to an enzyme to catalyze a certain reaction. ...

RNA can also act as a hereditary molecule, which encouraged Walter Gilbert to propose that in the past, the cell used RNA as both the genetic material and the structural and catalytic molecule, rather than dividing these functions between DNA and protein as they are today. This hypothesis became known as the "RNA world hypothesis" of the origin of life. Walter Gilbert Walter Gilbert (born March 21, 1932) is an American physicist, biochemist,and molecular biology pioneer. ... Drawing of the structure of cork as it appeared under the microscope to Robert Hooke from Micrographia which is the origin of the word cell being used to describe the smallest unit of a living organism Cells in culture, stained for keratin (red) and DNA (green) The cell is the... The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ... A representation of the 3D structure of myoglobin showing coloured alpha helices. ... RNA with its nitrogenous bases to the left and DNA to the right. ... For the definition, see Life. ...

If ribozymes were the first molecular machines used by early life, then today's remaining ribozymes -- such as the ribosome machinery -- could be considered living fossils of a life based primarily on nucleic acids. This article or section does not adequately cite its references or sources. ...

A recent test-tube study of prion folding suggests that an RNA may catalyze the pathological protein conformation in the manner of a chaperone enzyme.^[8] A prion (IPA: [1] ) — short for proteinaceous infectious particle (-on by analogy to virion) — is a type of infectious agent composed only of protein. ... Protein before and after folding. ... In chemistry, a chemical conformation is the spatial arrangement of atoms in a molecule. ...

Known ribozymes

Naturally occurring ribozymes include:

• Peptidyl transferase 23S rRNA
• RNase P
• Group I and Group II introns
• GIR1 branching ribozyme^[9]
• Leadzyme - Although initially created in vitro, natural examples have been found
• Hairpin ribozyme
• Hammerhead ribozyme
• HDV ribozyme
• Mammalian CPEB3 ribozyme
• VS ribozyme
• glmS ribozyme
• CoTC ribozyme

Ribosomal RNA (rRNA), a type of RNA synthesized in the nucleolus by RNA Pol I, is the central component of the ribosome, the protein manufacturing machinery of all living cells. ... Crystal structure of RNase P with substrate tRNA (green), PDB 2A64 Ribonuclease P (RNase P) is a type of Ribonuclease and is currently under heavy research. ... Diagram of the location of introns and exons within a gene. ... This page is a candidate for speedy deletion. ...

Artificial ribozymes

Since the discovery of ribozymes that exist in living organisms, there has been interest in the study of new synthetic ribozymes made in the laboratory. For example, artificially-produced self-cleaving RNAs that have good enzymatic activity have been produced. Tang and Breaker^[10] isolated self-cleaving RNAs by in vitro selection of RNAs originating from random-sequence RNAs. Some of the synthetic ribozymes that were produced had novel structures, while some were similar to the naturally occurring hammerhead ribozyme.

The techniques used to discover artificial ribozymes involve Darwinian evolution. This approach takes advantage of RNA's dual nature as both a catalyst and an informational polymer, making it easy for an investigator to produce vast populations of RNA catalysts using polymerase enzymes. The ribozymes are mutated by reverse transcibing them with reverse transcriptase into various cDNA and amplified with mutagenic PCR. The selection parameters in these experiments often differ. One approach for selecting a ligase ribozyme involves using biotin tags, which are covalently linked to the substrate. If a molecule possesses the desired ligase activity, a streptavidin matrix can be used to recover the active molecules. ITaq DNA polymerase A polymerase (EC 2. ... In biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into double-stranded DNA. Normal transcription involves the synthesis of RNA from DNA, hence reverse transcription is the reverse of this. ... In genetics, complementary DNA (cDNA) is single-stranded DNA synthesized from a mature mRNA template. ... Vitamin H redirects here. ... Streptavidin (less commonly spelled streptavidine) is a tetrameric protein purified from Streptomyces avidinii that binds very tightly to the vitamin biotin with a dissociation constant (Kd) of ~ 10^(–15) M. This is one of the strongest biochemical interactions known, and is widely taken advantage of in scientific laboratories. ...

See also

• Deoxyribozyme
• Spiegelman Monster
• Catalysis
• Enzyme
• RNA world hypothesis
• Peptide nucleic acid
• Nucleic acid analogues

Deoxyribozymes or DNA enzymes or catalytic DNA, or DNAzymes are DNA molecules with catalytic action. ... Spiegelman Monster is a RNA chain of only 220 nucleotides which is able to reproduce. ... Catalyst redirects here. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... RNA with its nitrogenous bases to the left and DNA to the right. ... PNA can also refer to the Palestinian National Authority or Pakistan National Alliance. ... Nucleic acid analogues are compounds structurally similar to naturally occuring RNA and DNA, used as a research tool in molecular biology and/or as cure in medicine. ...

References

1. ^ Johnston W, Unrau P, Lawrence M, Glasner M, Bartel D (2001). "RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension". Science 292 (5520): 1319-25. PMID 11358999.
2. ^ Zaher HS, Unrau P (2007). "Selection of an improved RNA polymerase ribozyme with superior extension and fidelity". RNA 13 (7): 1017-26. PMID 17586759.
3. ^ Hean J and Weinberg MS (2008). "The Hammerhead Ribozyme Revisited: New Biological Insights for the Development of Therapeutic Agents and for Reverse Genomics Applications", RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity. Caister Academic Press. ISBN 978-1-904455-25-7. 
4. ^ Enzyme definition Dictionary.com Accessed 6 April 2007
5. ^ Carl Woese, The Genetic Code (New York: Harper and Row, 1967).
6. ^ The Nobel Prize in Chemistry 1989 was awarded to Thomas R. Cech and Sidney Altman "for their discovery of catalytic properties of RNA".
7. ^ RNA Catalysis (Jan 2007). http://adsabs.harvard.edu/abs/1984OrLi...14..291V. Retrieved on 2007-08-04.
8. ^ "Prion protein conversion in vitro" by S. Supattapone (2004) in Journal of Molecular Medicine Volume 82, pages 348-356. Entrez PubMed 15014886
9. ^ Nielsen H, Westhof E, Johansen S (2005). "An mRNA is capped by a 2', 5' lariat catalyzed by a group I-like ribozyme". Science 309 (5740): 1584–7. doi:10.1126/science.1113645. PMID 16141078.
10. ^ Jin Tang and Ronald R. Breaker (1997). "Structural diversity of self-cleaving ribozymes". Proceedings of the National Academy of Sciences 97 (11): 5784-5789. PMID 10823936.

Thomas R. Cech received Nobel Prize in 1989 because he discovered the catalytic properties of RNA with Sidney Altman. ... Sidney Altman Sidney Altman (born May 7, 1939) is a Canadian-born molecular biologist, who is currently the Sterling Professor of Molecular, Cellular, and Developmental Biology and Chemistry at Yale University. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 216th day of the year (217th in leap years) in the Gregorian calendar. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

External links

• Ribozyme structures and mechanisms
• Directed evolution of nucleic acid enzymes.
• De novo synthesis and development of an RNA enzyme
• RNA catalysis evolutionary insight
• RNA catalysis