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Journal articles on the topic 'Ribozym'

Author: Grafiati

Published: 4 June 2021

Last updated: 27 January 2023

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1

Piganeau, Nicolas, Andreas Jenne, Vincent Thuillier, and Michael Famulok. "Ein durch Doxycyclin reguliertes allosterisches Ribozym." Angewandte Chemie 112, no. 23 (2000): 4538–42. http://dx.doi.org/10.1002/1521-3757(20001201)112:23<4538::aid-ange4538>3.0.co;2-2.

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2

Piganeau, Nicolas, Andreas Jenne, Vincent Thuillier, and Michael Famulok. "Ein durch Doxycyclin reguliertes allosterisches Ribozym." Angewandte Chemie 113, no. 19 (2001): 3612. http://dx.doi.org/10.1002/1521-3757(20011001)113:19<3612::aid-ange11113612>3.0.co;2-r.

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3

Ohkawa, J., N. Yuyama, Y. Takebe, S. Nishikawa, and K. Taira. "Importance of independence in ribozyme reactions: kinetic behavior of trimmed and of simply connected multiple ribozymes with potential activity against human immunodeficiency virus." Proceedings of the National Academy of Sciences 90, no. 23 (1993): 11302–6. http://dx.doi.org/10.1073/pnas.90.23.11302.

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The kinetic behavior of ribozymes derived from two types of multiple-ribozyme expression vector were examined. In some cases, multiple ribozymes were expressed as a single RNA molecule and all the ribozymes were simply connected in tandem (connected type). In other cases, multiple ribozymes were flanked by cis-acting ribozymes at both their 5' and 3' ends so that, upon transcription, multiple ribozymes were trimmed at both their 5' and 3' ends, with resultant liberation of multiple independent ribozymes (shotgun type). When levels of ribozyme expression were examined for the shotgun-type vecto

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4

Kisich, Kevin O., Robert W. Malone, Paul A. Feldstein та Kent L. Erickson. "Specific Inhibition of Macrophage TNF-α Expression by In Vivo Ribozyme Treatment". Journal of Immunology 163, № 4 (1999): 2008–16. http://dx.doi.org/10.4049/jimmunol.163.4.2008.

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Abstract The overproduction of the cytokine TNF-α is associated with inflammatory and autoimmune diseases. We have developed a means to block TNF-α production with ribozymes directed against TNF-α mRNA to selectively inhibit its production in vitro and in vivo. Following cationic lipid-mediated delivery to peritoneal murine macrophages in culture, anti-TNF-α ribozymes were more effective inhibitors of TNF-α secretion than catalytically inactive ribozyme controls. Inhibition of TNF-α secretion was proportional to the concentration of ribozyme administered, with an IC50 of ∼10 nM. After i.p. inj

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5

Wieland, Markus, and Jörg S. Hartig. "Vom Inhibitor zum Aktivator: ein Hammerhead-Ribozym unter der Kontrolle eines G-Quartetts." Angewandte Chemie 118, no. 35 (2006): 6007–10. http://dx.doi.org/10.1002/ange.200600909.

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6

Lieber, A., and M. Strauss. "Selection of efficient cleavage sites in target RNAs by using a ribozyme expression library." Molecular and Cellular Biology 15, no. 1 (1995): 540–51. http://dx.doi.org/10.1128/mcb.15.1.540.

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Inactivation of gene expression by antisense mechanisms in general and by ribozymes in particular is a powerful technique for studying the function of a gene product. We have designed a strategy for expression of ribozymes, for selection of accessible cleavage sites in target RNAs, and for isolation of ribozymes from a library of random sequences flanking the unique sequence of a hammerhead. The expression cassette for ribozyme genes is based on adenovirus-associated RNA. Alternatively, we used polymerase III or the T7 phage transcription machinery. The ribozyme sequences are positioned in the

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7

Castanotto, D., J. R. Li, A. Michienzi, et al. "Intracellular ribozyme applications." Biochemical Society Transactions 30, no. 6 (2002): 1140–45. http://dx.doi.org/10.1042/bst0301140.

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The exquisite target selectivity of trans-acting ribozymes has fostered their use as potential therapeutic agents and tools for down-regulating cellular transcripts. In living cells, free diffusion of RNAs is extremely limited, if it exists at all. Thus, getting ribozymes to base-pair with their cognate targets requires co-localizing the ribozyme transcript with the target RNA. In addition, not all sites along a given target RNA are equally accessible to ribozyme base pairing. Cellular proteins greatly influence the trafficking and structure of RNA, and therefore making ribozymes work effectiv

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8

Fiola, Karine, Jean-Pierre Perreault, and Benoit Cousineau. "Gene Targeting in the Gram-Positive Bacterium Lactococcus lactis, Using Various Delta Ribozymes." Applied and Environmental Microbiology 72, no. 1 (2006): 869–79. http://dx.doi.org/10.1128/aem.72.1.869-879.2006.

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ABSTRACT The trans-acting antigenomic delta ribozyme, isolated from the human hepatitis delta virus, was shown to be highly stable and active in vitro, as well as in mammalian cell lines. However, the stability and gene-targeting competence of this small ribozyme have not been studied previously in bacterial cells. In this paper we describe the use of two variants of the trans-acting antigenomic delta ribozyme targeting the abundant EF-Tu mRNA in the industrially important gram-positive bacterium Lactococcus lactis. These two delta ribozyme variants were expressed at significant levels and wer

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9

Aigner, A., and F. Czubayko. "Bioaktive Ribozym/Polyethylenimin-Komplexe: Ein neues Verfahren zum effizienten und spezifischen Targeting tumorrelevanter Genprodukte." Chemie Ingenieur Technik 74, no. 5 (2002): 714–15. http://dx.doi.org/10.1002/1522-2640(200205)74:5<714::aid-cite1111714>3.0.co;2-#.

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10

Lilley, David M. J. "Catalysis by the nucleolytic ribozymes." Biochemical Society Transactions 39, no. 2 (2011): 641–46. http://dx.doi.org/10.1042/bst0390641.

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The nucleolytic ribozymes use general acid–base catalysis to contribute significantly to their rate enhancement. The VS (Varkud satellite) ribozyme uses a guanine and an adenine nucleobase as general base and acid respectively in the cleavage reaction. The hairpin ribozyme is probably closely similar, while the remaining nucleolytic ribozymes provide some interesting contrasts.

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11

Waninger, Shani, Kelli Kuhen, Xiuyuan Hu, Jon E. Chatterton, Flossie Wong-Staal, and Hengli Tang. "Identification of Cellular Cofactors for Human Immunodeficiency Virus Replication via a Ribozyme-Based Genomics Approach." Journal of Virology 78, no. 23 (2004): 12829–37. http://dx.doi.org/10.1128/jvi.78.23.12829-12837.2004.

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ABSTRACT Ribozymes are small, catalytic RNA molecules that can be engineered to down-regulate gene expression by cleaving specific mRNA. Here we report the selection of hairpin ribozymes that inhibit human immunodeficiency virus (HIV) replication from a combinatorial ribozyme library. We identified a total of 17 effective ribozymes, each capable of inhibiting HIV infection of human CD4+ cells. These ribozymes target diverse steps of the viral replication cycle, ranging from entry to transcription. One ribozyme suppressed HIV integration and transcription by inhibiting the expression of the Ku8

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12

Scott, William G. "Biophysical and biochemical investigations of RNA catalysis in the hammerhead ribozyme." Quarterly Reviews of Biophysics 32, no. 3 (1999): 241–84. http://dx.doi.org/10.1017/s003358350000353x.

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1. How do ribozymes work? 2412. The hammerhead RNA as a prototype ribozyme 2422.1 RNA enzymes 2422.2 Satellite self-cleaving RNAs 2422.3 Hammerhead RNAs and hammerhead ribozymes 2443. The chemical mechanism of hammerhead RNA self-cleavage 2463.1 Phosphodiester isomerization via an SN2(P) reaction 2473.2 The canonical role of divalent metal ions in the hammerhead ribozyme reaction 2513.3 The hammerhead ribozyme does not actually require metal ions for catalysis 2543.4 Hammerhead RNA enzyme kinetics 2574. Sequence requirements for hammerhead RNA self-cleavage 2604.1 The conserved core, mutagenes

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13

Arriola, Joshua T., and Ulrich F. Müller. "A combinatorial method to isolate short ribozymes from complex ribozyme libraries." Nucleic Acids Research 48, no. 20 (2020): e116-e116. http://dx.doi.org/10.1093/nar/gkaa834.

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Abstract In vitro selections are the only known methods to generate catalytic RNAs (ribozymes) that do not exist in nature. Such new ribozymes are used as biochemical tools, or to address questions on early stages of life. In both cases, it is helpful to identify the shortest possible ribozymes since they are easier to deploy as a tool, and because they are more likely to have emerged in a prebiotic environment. One of our previous selection experiments led to a library containing hundreds of different ribozyme clusters that catalyze the triphosphorylation of their 5′-terminus. This selection

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14

Ramezani, A., W. Marhin, M. Weerasinghe, and S. Joshi. "A rapid and efficient system for screening HIV-1 Pol mRNA-specific ribozymes." Canadian Journal of Microbiology 43, no. 1 (1997): 92–96. http://dx.doi.org/10.1139/m97-013.

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Hammerhead ribozymes are potentially important tools for suppressing intracellular expression of unwanted RNAs. However, the reports that exist on their activity against different targets have described mixed success. As an initial step towards developing a rapid and effective system for in vivo testing of ribozymes, two human immunodeficiency virus type-1 (HIV-1) polymerase (Pol) mRNA-specific ribozymes, RzProdirected against the protease (Pro) coding region and RzRTdirected against the reverse transcriptase (RT) coding region, were designed and tested in Escherichia coli. Both ribozymes disp

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15

Zhang, Zhenxi, and John M. Burke. "Inhibition of Viral Replication by Ribozyme: Mutational Analysis of the Site and Mechanism of Antiviral Activity." Journal of Virology 79, no. 6 (2005): 3728–36. http://dx.doi.org/10.1128/jvi.79.6.3728-3736.2005.

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ABSTRACT A controlled mutational study was used to determine the site and mechanism of the antiviral action of ribozymes that inhibit Sindbis virus replication. A hairpin ribozyme targeting G575 of the Sindbis virus genomic RNA was designed and cloned into a minimized alphavirus amplicon vector. Cells that were stably transfected with this construct expressed low levels of a constitutive transcript containing the ribozyme plus recognition sequences for Sindbis RNA replicase. Upon infection, the ribozyme transcript was amplified to high levels by the viral replicase, resulting in decreased vira

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16

Takagi, Y., E. Suyama, H. Kawasaki, M. Miyagishi, and K. Taira. "Mechanism of action of hammerhead ribozymes and their applications in vivo: rapid identification of functional genes in the post-genome era by novel hybrid ribozyme libraries." Biochemical Society Transactions 30, no. 6 (2002): 1145–49. http://dx.doi.org/10.1042/bst0301145.

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A hammerhead ribozyme was demonstrated to be a metalloenzyme. By controlling the metal-binding ability of the hammerhead ribozyme in the presence or absence of a specific sequence of interest, we engineered an allosterically controllable ribozyme, designated the maxizyme. Hybrid ribozymes were then constructed by coupling the site-specific cleavage activity of a hammerhead ribozyme with the unwinding activity of an endogenous RNA helicase. This leads to extremely efficient cleavage of target mRNA, not only in vitro, but also in vivo, and eliminates one of the major problems arising in the appl

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17

Bendixsen, Devin P., Tanner B. Pollock, Gianluca Peri, and Eric J. Hayden. "Experimental Resurrection of Ancestral Mammalian CPEB3 Ribozymes Reveals Deep Functional Conservation." Molecular Biology and Evolution 38, no. 7 (2021): 2843–53. http://dx.doi.org/10.1093/molbev/msab074.

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Abstract Self-cleaving ribozymes are genetic elements found in all domains of life, but their evolution remains poorly understood. A ribozyme located in the second intron of the cytoplasmic polyadenylation binding protein 3 gene (CPEB3) shows high sequence conservation in mammals, but little is known about the functional conservation of self-cleaving ribozyme activity across the mammalian tree of life or during the course of mammalian evolution. Here, we use a phylogenetic approach to design a mutational library and a deep sequencing assay to evaluate the in vitro self-cleavage activity of num

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18

Ferré-D'Amaré, Adrian R. "Use of a coenzyme by the glmS ribozyme-riboswitch suggests primordial expansion of RNA chemistry by small molecules." Philosophical Transactions of the Royal Society B: Biological Sciences 366, no. 1580 (2011): 2942–48. http://dx.doi.org/10.1098/rstb.2011.0131.

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The glmS ribozyme-riboswitch is the first known example of a naturally occurring catalytic RNA that employs a small molecule as a coenzyme. Binding of glucosamine-6-phosphate (GlcN6P) activates self-cleavage of the bacterial ribozyme, which is part of the mRNA encoding the metabolic enzyme GlcN6P-synthetase. Cleavage leads to negative feedback regulation. GlcN6P binds in the active site of the ribozyme, where its amine could function as a general acid and electrostatic catalyst. The ribozyme is pre-folded but inactive in the absence of GlcN6P, demonstrating it has evolved strict dependence on

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19

Koseki, Shiori, Tsuyoshi Tanabe, Kenzaburo Tani, et al. "Factors Governing the Activity In Vivo of Ribozymes Transcribed by RNA Polymerase III." Journal of Virology 73, no. 3 (1999): 1868–77. http://dx.doi.org/10.1128/jvi.73.3.1868-1877.1999.

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ABSTRACT In order to determine the parameters that govern the activity of a ribozyme in vivo, we made a systematic analysis of chimeric tRNAVal ribozymes by measuring their cleavage activities in vitro as well as the steady-state levels of transcripts, the half-lives of transcribed tRNAVal ribozymes, and their activities in both HeLa and H9 cells. These analyses were conducted by the use of transient expression systems in HeLa cells and stable transformants that express ribozymes. Localization of transcripts appeared to be determined by the higher-order structure of each transcribed tRNAVal ri

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20

Horan, Lucas. "Ribozyme mediated alternative poly-adenylation of the inhibitory NK-ligand Clec2d. (116.36)." Journal of Immunology 186, no. 1_Supplement (2011): 116.36. http://dx.doi.org/10.4049/jimmunol.186.supp.116.36.

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Abstract Structured RNAs that are embedded in mature mRNAs have been shown to effectively regulate gene expression in a variety of single-celled organisms. Our discovery of conserved mammalian hammerhead ribozymes located in the 3‘-untranslated regions (UTR) of certain C-type lectin type II (CLEC2) genes suggests that a similar form of regulation may also be operative in more complex organisms. The ribozyme-associated Clec2d gene codes for a broadly expressed cell-surface ligand, CLEC2D, that is involved in suppressing natural killer cell-mediated lysis of CLEC2D expressing cells. Published da

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21

Cantor, G. H., T. F. McElwain, T. A. Birkebak, and G. H. Palmer. "Ribozyme cleaves rex/tax mRNA and inhibits bovine leukemia virus expression." Proceedings of the National Academy of Sciences 90, no. 23 (1993): 10932–36. http://dx.doi.org/10.1073/pnas.90.23.10932.

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Bovine leukemia virus (BLV) encodes at least two regulatory proteins, Rex and Tax. Tax, the transactivating protein, stimulates the long terminal repeat to promote viral transcription and may be involved in tumorigenesis. Rex is involved in the transition from early expression of regulatory proteins to later expression of viral structural proteins. We have targeted ribozymes against the mRNA encoding Rex and Tax. The ribozymes consist of the hammer-head catalytic motif flanked by antisense sequences that hybridize with the complementary rex/tax mRNA. To evaluate cleavage in a cell-free system,

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22

Olzog, V. Janett, and Christina E. Weinberg. "Nutzung von RNA-seq zur Detektion aktiver Ribozyme in Zellextrakten." BIOspektrum 28, no. 3 (2022): 261–63. http://dx.doi.org/10.1007/s12268-022-1747-0.

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AbstractSelf-cleaving ribozymes are catalytic RNAs that cleave their own sugar phosphate backbone site-specifically. While most ribozyme classes were discovered serendipitously, only four classes were found through targeted methods. We developed an RNA-seq-based strategy, called cyPhyRNA-seq, to capture both ribozyme cleavage fragments in a targeted fashion. This method can be used to study ribozyme activity on a global scale and has the potential to uncover new self-cleaving ribozyme classes.

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23

Akagi, Junya, Takahiro Yamada, Kumi Hidaka, et al. "An RNA Triangle with Six Ribozyme Units Can Promote a Trans-Splicing Reaction through Trimerization of Unit Ribozyme Dimers." Applied Sciences 11, no. 6 (2021): 2583. http://dx.doi.org/10.3390/app11062583.

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Ribozymes are catalytic RNAs that are attractive platforms for the construction of nanoscale objects with biological functions. We designed a dimeric form of the Tetrahymena group I ribozyme as a unit structure in which two ribozymes were connected in a tail-to-tail manner with a linker element. We introduced a kink-turn motif as a bent linker element of the ribozyme dimer to design a closed trimer with a triangular shape. The oligomeric states of the resulting ribozyme dimers (kUrds) were analyzed biochemically and observed directly by atomic force microscopy (AFM). Formation of kUrd oligomer

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24

Lilley, David M. J. "Mechanisms of RNA catalysis." Philosophical Transactions of the Royal Society B: Biological Sciences 366, no. 1580 (2011): 2910–17. http://dx.doi.org/10.1098/rstb.2011.0132.

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Ribozymes are RNA molecules that act as chemical catalysts. In contemporary cells, most known ribozymes carry out phosphoryl transfer reactions. The nucleolytic ribozymes comprise a class of five structurally-distinct species that bring about site-specific cleavage by nucleophilic attack of the 2′-O on the adjacent 3′-P to form a cyclic 2′,3′-phosphate. In general, they will also catalyse the reverse reaction. As a class, all these ribozymes appear to use general acid–base catalysis to accelerate these reactions by about a million-fold. In the Varkud satellite ribozyme, we have shown that the

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25

Siddika, Mst Ayesha, Takahiro Yamada, Risako Aoyama, et al. "Catalytic RNA Oligomers Formed by Co-Oligomerization of a Pair of Bimolecular RNase P Ribozymes." Molecules 27, no. 23 (2022): 8298. http://dx.doi.org/10.3390/molecules27238298.

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Naturally occurring ribozymes with a modular architecture are promising platforms for construction of RNA nanostructures because modular redesign enables their oligomerization. The resulting RNA nanostructures can exhibit the catalytic function of the parent ribozyme in an assembly dependent manner. In this study, we designed and constructed open-form oligomers of a bimolecular form of an RNase P ribozyme. The ribozyme oligomers were analyzed biochemically and by atomic force microscopy (AFM).

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26

Collins, R. A. "The Neurospora Varkud satellite ribozyme." Biochemical Society Transactions 30, no. 6 (2002): 1122–26. http://dx.doi.org/10.1042/bst0301122.

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Presented is a review of the discovery and characterization of the Neurospora Varkud satellite ribozyme. It outlines the approaches and observations that have led to our current level of understanding of the structure and function of this ribozyme, and highlights its distinctive features compared with other naturally occurring small ribozymes.

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27

Korman, Arthur, Huabing Sun, Boyang Hua, et al. "Light-controlled twister ribozyme with single-molecule detection resolves RNA function in time and space." Proceedings of the National Academy of Sciences 117, no. 22 (2020): 12080–86. http://dx.doi.org/10.1073/pnas.2003425117.

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Small ribozymes such asOryza sativatwister spontaneously cleave their own RNA when the ribozyme folds into its active conformation. The coupling between twister folding and self-cleavage has been difficult to study, however, because the active ribozyme rapidly converts to product. Here, we describe the synthesis of a photocaged nucleotide that releases guanosine within microseconds upon photosolvolysis with blue light. Application of this tool toO. sativatwister achieved the spatial (75 µm) and temporal (≤30 ms) control required to resolve folding and self-cleavage events when combined with si

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28

Ciesiolka, J., J. Wrzesinski, M. Legiewicz, B. Smólska, and M. Dutkiewicz. "Ribozymes of the hepatitis delta virus: recent findings on their structure, mechanism of catalysis and possible applications." Acta Biochimica Polonica 48, no. 2 (2001): 409–18. http://dx.doi.org/10.18388/abp.2001_3925.

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Although the delta ribozymes have been studied for more than ten years the most important information concerning their structure and mechanism of catalysis were only obtained very recently. The crystal structure of the genomic delta ribozyme turns out to be an excellent example of the extraordinary properties of RNA molecules to fold into uniquely compact structures. Details of the X-ray structure have greatly stimulated further studies on the folding of the ribozymes into functionally active molecules as well as on the mechanism of RNA catalysis. The ability of the delta ribozymes to carry ou

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29

Nomura, Yoko, and Yohei Yokobayashi. "Systematic minimization of RNA ligase ribozyme through large-scale design-synthesis-sequence cycles." Nucleic Acids Research 47, no. 17 (2019): 8950–60. http://dx.doi.org/10.1093/nar/gkz729.

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Abstract Template-directed RNA ligation catalyzed by an RNA enzyme (ribozyme) is a plausible and important reaction that could have been involved in transferring genetic information during prebiotic evolution. Laboratory evolution experiments have yielded several classes of ligase ribozymes, but their minimal sequence requirements remain largely unexplored. Because selection experiments strongly favor highly active sequences, less active but smaller catalytic motifs may have been overlooked in these experiments. We used large-scale DNA synthesis and high-throughput ribozyme assay enabled by de

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30

Fedor, M. J. "The catalytic mechanism of the hairpin ribozyme." Biochemical Society Transactions 30, no. 6 (2002): 1109–15. http://dx.doi.org/10.1042/bst0301109.

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Evidence that hairpin ribozymes function in the absence of bivalent cation cofactors suggests that active site nucleobases might participate directly in catalytic chemistry. We have adopted an abasic ribozyme rescue strategy to begin to dissect the roles of specific nucleobases in hairpin ribozyme activity. Loss of one active site nucleobase, G8, could be compensated by providing certain nucleobases and nucleobase analogues in solution. Comparison of the biochemical and structural features that are shared among small molecules that mediate rescue provides a new perspective on potential mechani

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31

Sripathi, Kamali N., Pavel Banáš, Kamila Réblová, Jiří Šponer, Michal Otyepka, and Nils G. Walter. "Wobble pairs of the HDV ribozyme play specific roles in stabilization of active site dynamics." Physical Chemistry Chemical Physics 17, no. 8 (2015): 5887–900. http://dx.doi.org/10.1039/c4cp05083e.

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32

Cech, T. R. "Ribozymes, the first 20 years." Biochemical Society Transactions 30, no. 6 (2002): 1162–66. http://dx.doi.org/10.1042/bst0301162.

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In 1982 we reported the first catalytic RNA or ribozyme: the self-splicing intron of the Tetrahymena pre-rRNA. Additional examples of natural ribozymes were soon found, and research in the field focused on their enzymic mechanism and secondary and tertiary structure. Ribozymes identified through in vitro selection extended the repertoire of RNA catalysis. Two directions of current and future interest are the determination of atomic-resolution structures of large ribozymes by X-ray crystallography and the structural and mechanistic analysis of complexes of ribozymes with protein facilitators of

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33

Leopold, LH, SK Shore, TA Newkirk, RM Reddy, and EP Reddy. "Multi-unit ribozyme-mediated cleavage of bcr-abl mRNA in myeloid leukemias." Blood 85, no. 8 (1995): 2162–70. http://dx.doi.org/10.1182/blood.v85.8.2162.bloodjournal8582162.

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Chronic myelogenous leukemia is characterized by the Philadelphia chromosome, which at the molecular level results from the fusion of the bcr gene on chromosome 22 and the abl gene on chromosome 9. The bcr-abl fusion gene encodes a novel tyrosine kinase with transforming activity. In this study, we have synthesized a multi-unti ribozyme that targets bcr-abl mRNA. In vitro ribozyme cleavage reactions show increased cleavage efficiency of this multi-unit ribozyme compared with single or double ribozymes. The multiunit ribozyme was then transfected into murine myeloblasts transformed with the bcr

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34

Müller, Sabine, Bettina Appel, Darko Balke, Robert Hieronymus, and Claudia Nübel. "Thirty-five years of research into ribozymes and nucleic acid catalysis: where do we stand today?" F1000Research 5 (June 27, 2016): 1511. http://dx.doi.org/10.12688/f1000research.8601.1.

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Since the discovery of the first catalytic RNA in 1981, the field of ribozyme research has developed from the discovery of catalytic RNA motifs in nature and the elucidation of their structures and catalytic mechanisms, into a field of engineering and design towards application in diagnostics, molecular biology and medicine. Owing to the development of powerful protocols for selection of nucleic acid catalysts with a desired functionality from random libraries, the spectrum of nucleic acid supported reactions has greatly enlarged, and importantly, ribozymes have been accompanied by DNAzymes. C

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Lafontaine, D. A., D. G. Norman, and D. M. J. Lilley. "The structure and active site of the Varkud satellite ribozyme." Biochemical Society Transactions 30, no. 6 (2002): 1170–75. http://dx.doi.org/10.1042/bst0301170.

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The Varkud satellite ribozyme is the largest of the small nucleolytic ribozymes, and the only one for which there is no crystal structure. It can be divided into a trans-acting ribozyme, consisting of five helices organized by two three-way helical junctions, and a stem-loop substrate with which it interacts, primarily by tertiary interactions. We have determined the global fold of the ribozyme, and the manner by which it interacts with the substrate. The substrate interacts with a cleft formed between helices II and VI (organized by the lower helical junction), where it contacts the A730 loop

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36

Matsushita, Hiromichi, Masahiro Kizaki, Hiroyuki Kobayashi, et al. "Restoration of Retinoid Sensitivity by MDR1 Ribozymes in Retinoic Acid–Resistant Myeloid Leukemic Cells." Blood 91, no. 7 (1998): 2452–58. http://dx.doi.org/10.1182/blood.v91.7.2452.

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Abstract Complete remission is achieved in a high proportion of patients with acute promyelocytic leukemia (APL) after all-trans retinoic acid (RA) treatment, but most patients relapse and develop RA-resistant APL. We have previously reported that both RA-resistant HL-60 (HL-60R) and APL cells express P-glycoprotein and MDR1 transcripts; and these cells differentiate to mature granulocytes after culture with RA and P-glycoprotein antagonist. Ribozymes have been shown to be able to intercept a target RNA by catalytic activity. To address the role of MDR1 in overcoming RA-resistance in APL cells

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37

Matsushita, Hiromichi, Masahiro Kizaki, Hiroyuki Kobayashi, et al. "Restoration of Retinoid Sensitivity by MDR1 Ribozymes in Retinoic Acid–Resistant Myeloid Leukemic Cells." Blood 91, no. 7 (1998): 2452–58. http://dx.doi.org/10.1182/blood.v91.7.2452.2452_2452_2458.

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Complete remission is achieved in a high proportion of patients with acute promyelocytic leukemia (APL) after all-trans retinoic acid (RA) treatment, but most patients relapse and develop RA-resistant APL. We have previously reported that both RA-resistant HL-60 (HL-60R) and APL cells express P-glycoprotein and MDR1 transcripts; and these cells differentiate to mature granulocytes after culture with RA and P-glycoprotein antagonist. Ribozymes have been shown to be able to intercept a target RNA by catalytic activity. To address the role of MDR1 in overcoming RA-resistance in APL cells, we inve

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lyngstadaas, S. Petter. "Synthetic Hammerhead Ribozymes as Tools in Gene Expression." Critical Reviews in Oral Biology & Medicine 12, no. 6 (2001): 469–78. http://dx.doi.org/10.1177/10454411010120060201.

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The assessment of genetic controls for sequential developmental processes such as tooth formation and biomineralization is often difficult in transgenic "knockout" models, where phenotypes reflect only the permanent eradication of a gene, and reveal little about the dynamic range of expression for the gene(s) involved. One promising strategy to overcome this problem is through the use of ribozymes, a class of metalloenzymes made entirely of ribonucleic acid (RNA), that are capable of cleaving other RNA molecules in a catalytic fashion. Their activity can be targeted against specific mRNAs by s

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Burke, J. M. "Hairpin and hammerhead ribozymes: how different are they?" Biochemical Society Transactions 30, no. 6 (2002): 1116–19. http://dx.doi.org/10.1042/bst0301116.

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Recent experimental work on the hairpin and hammerhead ribozymes suggests that they have more similarities than previously suspected. Notably, each is now known to function as a true RNA catalyst, not requiring metal ions for folding or catalytic function. The active conformation of the hairpin ribozyme has been established by crystallography, and is well supported by biochemical and biophysical evidence that has identified conformational changes and key nucleotides required for catalysis. Analogous work is under way to establish the active structure of the hammerhead ribozyme.

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HENDRIX, Chris, Jozef ANNÉ, Bernard JORIS, Arthur VAN AERSCHOT, and Piet HERDEWIJN. "Selection of hammerhead ribozymes for optimum cleavage of interleukin 6 mRNA." Biochemical Journal 314, no. 2 (1996): 655–61. http://dx.doi.org/10.1042/bj3140655.

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Four GUC triplets in the coding region of the mRNA of interleukin 6 (IL-6) were examined for their suitability to serve as a target for hammerhead ribozyme-mediated cleavage. This selection procedure was performed with the intention to down-regulate IL-6 production as a potential treatment of those diseases in which IL-6 overexpression is involved. Hammerhead ribozymes and their respective short synthetic substrates (19-mers) were synthesized for these four GUC triplets. Notwithstanding the identical catalytic core sequences, the difference in base composition of the helices involved in substr

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Nguyen, Laura A., Jimin Wang, and Thomas A. Steitz. "Crystal structure of Pistol, a class of self-cleaving ribozyme." Proceedings of the National Academy of Sciences 114, no. 5 (2017): 1021–26. http://dx.doi.org/10.1073/pnas.1611191114.

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Small self-cleaving ribozymes have been discovered in all evolutionary domains of life. They can catalyze site-specific RNA cleavage, and as a result, they have relevance in gene regulation. Comparative genomic analysis has led to the discovery of a new class of small self-cleaving ribozymes named Pistol. We report the crystal structure of Pistol at 2.97-Å resolution. Our results suggest that the Pistol ribozyme self-cleavage mechanism likely uses a guanine base in the active site pocket to carry out the phosphoester transfer reaction. The guanine G40 is in close proximity to serve as the gene

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Hendry, Philip, Maxine J. McCall, and Trevor J. Lockett. "Influence of Helix Length on Cleavage Efficiency of Hammerhead Ribozymes." Australian Journal of Chemistry 58, no. 12 (2005): 851. http://dx.doi.org/10.1071/ch05196.

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The cleavage rates of RNA substrates by trans-acting, hammerhead ribozymes are controlled by interactions between helices I and II. The interactions are affected by the relative lengths of these two double helices and by unpaired nucleotides protruding beyond helix I, either in the substrate or the ribozyme strand. Maximum cleavage rates are observed for ribozyme–substrate complexes with three or more base pairs in helix II and six or less base pairs in helix I. However, for these helix combinations, rates fall sharply with unpaired nucleotides at the end of helix I. Cleavage rates by ribozyme

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Maurel, Marie-Christine, Fabrice Leclerc, Jacques Vergne, and Giuseppe Zaccai. "RNA Back and Forth: Looking through Ribozyme and Viroid Motifs." Viruses 11, no. 3 (2019): 283. http://dx.doi.org/10.3390/v11030283.

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Current cellular facts allow us to follow the link from chemical to biochemical metabolites, from the ancient to the modern world. In this context, the “RNA world” hypothesis proposes that early in the evolution of life, the ribozyme was responsible for the storage and transfer of genetic information and for the catalysis of biochemical reactions. Accordingly, the hammerhead ribozyme (HHR) and the hairpin ribozyme belong to a family of endonucleolytic RNAs performing self-cleavage that might occur during replication. Furthermore, regarding the widespread occurrence of HHRs in several genomes o

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Dai, Wei, Rong Zhou, Hong Yu, and Xiao-juan Li. "Inhibition of Hepatitis B Virus Replication and Expression in Vitro and in Vivo by the Hammerhead Ribozymes Targeted Different Sites." Infection International 1, no. 4 (2012): 206–10. http://dx.doi.org/10.1515/ii-2017-0029.

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Abstract Objective To develop an effective and specific medicine targeting hepatitis B virus (HBV) pregenome. Based on the identified accessible target sites for hammerhead ribozyme in our previous researches, a recombinant hepatitis delta virus (HDV) ribozyme was chosen and used to demonstrate the effective cleavage in vitro and in vivo. Methods Three hammerhead ribozymes for potential target sites (S, X and C genes) and co-expression plasmid (pTr-dB, pTdδ-dB, pTrX-dB and pTrC-dB) as well as four HDV-ribozyme chimera constructs with HBV (pTdXX, pTdXC, pTdSX and pTdSC) were severally chosen to

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Halatsch, Marc-Eric, Ursula Schmidt, Ingolf C. Bötefür, James F. Holland, and Takao Ohnuma. "Marked inhibition of glioblastoma target cell tumorigenicity in vitro by retrovirus-mediated transfer of a hairpin ribozyme against deletion-mutant epidermal growth factor messenger RNA." Journal of Neurosurgery 92, no. 2 (2000): 297–305. http://dx.doi.org/10.3171/jns.2000.92.2.0297.

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Object. The goal of this study was to evaluate the activity of certain hairpin ribozymes against deletion-mutant epidermal growth factor receptor (ΔEGFR) messenger (m)RNA in glioblastomas multiforme (GBMs). A distinct 801-bp deletion mutation associated with amplification of the EGFR gene is present in a large subgroup of primary GBMs and confers enhanced tumorigenicity in vivo. As a result of the deletion mutation, the fusion junction of the gene is created directly upstream of a GTA triplet, which is subsequently transcribed into a ribozyme target codon (GUA).Methods. In attempts to intercep

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Long, Meredith B., and Bruce A. Sullenger. "Evaluating Group I Intron Catalytic Efficiency in Mammalian Cells." Molecular and Cellular Biology 19, no. 10 (1999): 6479–87. http://dx.doi.org/10.1128/mcb.19.10.6479.

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ABSTRACT Recent reports have demonstrated that the group I ribozyme fromTetrahymena thermophila can performtrans-splicing reactions to repair mutant RNAs. For therapeutic use, such ribozymes must function efficiently when transcribed from genes delivered to human cells, yet it is unclear how group I splicing reactions are influenced by intracellular expression of the ribozyme. Here we evaluate the self-splicing efficiency of group I introns from transcripts expressed by RNA polymerase II in human cells to directly measure ribozyme catalysis in a therapeutically relevant setting. Intron-contain

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Ferré-D'Amaré, A. R., and P. B. Rupert. "The hairpin ribozyme: from crystal structure to function." Biochemical Society Transactions 30, no. 6 (2002): 1105–9. http://dx.doi.org/10.1042/bst0301105.

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The hairpin ribozyme is one of four known natural catalytic RNAs that carry out sequence-specific cleavage of RNA. It is of particular biochemical interest because, unlike ‘classic’ ribozymes, such as the group I intron, it appears not to employ metal ions as catalytic cofactors. We have determined the crystal structure of a hairpin-ribozyme-inhibitor complex at a resolution of 2.4 Å. The active site of the ribozyme results from docking of two irregular double helices. Docking results in major structural rearrangements of the helices, including a distortion of the substrate strand that brings

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DasGupta, Saurja, Kamila Nykiel, and Joseph A. Piccirilli. "The hammerhead self-cleaving motif as a precursor to complex endonucleolytic ribozymes." RNA 27, no. 9 (2021): 1017–24. http://dx.doi.org/10.1261/rna.078813.121.

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Connections between distinct catalytic RNA motifs through networks of mutations that retain catalytic function (neutral networks) were likely central to the evolution of biocatalysis. Despite suggestions that functional RNAs collectively form an interconnected web of neutral networks, little evidence has emerged to demonstrate the existence of such intersecting networks in naturally occurring RNAs. Here we show that neutral networks of two naturally occurring, seemingly unrelated endonucleolytic ribozymes, the hammerhead (HH) and hairpin (HP), intersect. Sequences at the intersection of these

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Lilley, David M. J. "Ribozymes: ancient and modern." Biochemist 37, no. 2 (2015): 4–8. http://dx.doi.org/10.1042/bio03702004.

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Ribozymes are catalytic RNA molecules, enzymes made of RNA. They were probably the key to the early development of life on the planet in the RNA world, but are still present in contemporary cells, carrying out some of the most important reactions such as the synthesis of proteins. Although clearly not as well suited to this role as proteins, ribozymes nevertheless can achieve some impressive rate enhancements. Mechanistic and structural studies have revealed much of the way that this is achieved. But perhaps even more interesting ribozyme species may still await discovery.

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Przybilski, Rita, and Christian Hammann. "Idiosyncratic cleavage and ligation activity of individual hammerhead ribozymes and core sequence variants thereof." Biological Chemistry 388, no. 7 (2007): 737–41. http://dx.doi.org/10.1515/bc.2007.065.

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AbstractThe hammerhead ribozyme is a small RNA endonuclease found in sub-viral plant pathogens, in transcripts from certain animal satellite DNAs and encoded at distinct loci ofArabidopsis thaliana. Kinetic analyses of tertiary stabilised ribozymes from peach latent mosaic viroid (PLMVd),Schistosoma mansoniandA. thalianarevealed a ten-fold difference in cleavage rates. Core nucleotide variations affected cleavage reactions least in theA. thalianaribozyme, and most in theS. mansoniribozyme. The reverse ligation reaction was catalysed efficiently by the PLMVd andA. thalianaribozymes. The differe

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