Modulation of Catalytic RNA Biological Activity by Small Molecule Effectors

Vourekas, Anastassios; Kalavrizioti, Dimitra; Stathopoulos, Constantinos; Drainas, Denis

doi:10.2174/138955706778195199

Cited by 5 publications

(5 citation statements)

References 79 publications

(91 reference statements)

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“…For example, neomycin was found to compete with the Rev protein for HIV RRE, resulting in attenuated HIV replication in tissue culture cells . Moreover, aminoglycosides also act as inhibitors of several ribozymes, including hammerhead, group I introns, and RNase P . The molecular structure of aminoglycosides is characterized by a highly conserved diaminocyclohexitol termed 2-deoxystreptamine and suggests an essential role in binding to RNA.…”

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confidence: 99%

A Short and Scalable Route to Orthogonally O-Protected 2-Deoxystreptamine

et al. 2007

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A seven-step synthesis of orthogonally O-protected 2-deoxy-streptamine has been developed from readily available neomycin, with an overall yield of 28%. Key chemical transformations include a chemoselective glycosidic bond hydrolysis and two regioselective protective group manipulations involving acetylation and deacetylation. The synthetic route is amenable to scale-up for the production of multigram quantities of enantiopure and orthogonally O-protected 2-deoxystreptamine, a versatile scaffold for the generation of libraries of RNA-targeting ligands.

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confidence: 99%

A Short and Scalable Route to Orthogonally O-Protected 2-Deoxystreptamine

et al. 2007

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“…The description of the secondary structure of the D. discoideum RNase P RNA may provide information on the mode of action of small molecule effectors, such as protein synthesis inhibitors and retinoids, which have been reported to exhibit strong The standard errors of the curve fits shown in Figure 8 are indicated in the estimates of K m and V max . inhibitory effect on eukaryotic RNase P activity (50)(51)(52). As already mentioned, efforts for identifying a ribonucleolytic activity of the RNase P RNA transcript in vitro that can be reliably characterized were unsuccessful.…”

Section: Discussionmentioning

confidence: 99%

Domain Architecture of the DRpp29 Protein and Its Interaction with the RNA Subunit of Dictyostelium discoideum RNase P

et al. 2010

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Dictyostelium discoideum nuclear RNase P is a ribonucleoprotein complex that displays similarities with its counterparts from higher eukaryotes such as the human enzyme, but at the same time it retains distinctive characteristics. In the present study, we report the molecular cloning and interaction details of DRpp29 and RNase P RNA, two subunits of the RNase P holoenzyme from D. discoideum. Electrophoretic mobility shift assays exhibited that DRpp29 binds specifically to the RNase P RNA subunit, a feature that was further confirmed by the molecular modeling of the DRpp29 structure. Moreover, deletion mutants of DRpp29 were constructed in order to investigate the domains of DRpp29 that contribute to and/or are responsible for the direct interaction with the D. discoideum RNase P RNA. A eukaryotic specific, lysine- and arginine-rich region was revealed, which seems to facilitate the interaction between these two subunits. Furthermore, we tested the ability of wild-type and mutant DRpp29 to form active RNase P enzymatic particles with the Escherichia coli RNase P RNA.

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“…Moreover, RNAs and RNA-protein complexes from pathogens are common therapeutical targets (e.g., ribosome is one of the main antibiotic targets in the cell) (18). Clearly, the study of functional RNAs and, more particularly, ribozymes advances our knowledge on the evolutionary history of biomolecules and contributes to the development of research and therapeutical tools.…”

Section: Introductionmentioning

confidence: 99%

Insights into functional modulation of catalytic RNA activity

et al. 2008

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SummaryRNA molecules play critical roles in cell biology, and novel findings continuously broaden their functional repertoires. Apart from their well-documented participation in protein synthesis, it is now apparent that several noncoding RNAs (i.e., micro-RNAs and riboswitches) also participate in the regulation of gene expression. The discovery of catalytic RNAs had profound implications on our views concerning the evolution of life on our planet at a molecular level. A characteristic attribute of RNA, probably traced back to its ancestral origin, is the ability to interact with and be modulated by several ions and molecules of different sizes. The inhibition of ribosome activity by antibiotics has been extensively used as a therapeutical approach, while activation and substrate-specificity alteration have the potential to enhance the versatility of ribozyme-based tools in translational research. In this review, we will describe some representative examples of such modulators to illustrate the potential of catalytic RNAs as tools and targets in research and clinical approaches.

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Modulation of Catalytic RNA Biological Activity by Small Molecule Effectors

Cited by 5 publications

References 79 publications

A Short and Scalable Route to Orthogonally O-Protected 2-Deoxystreptamine

A Short and Scalable Route to Orthogonally O-Protected 2-Deoxystreptamine

Domain Architecture of the DRpp29 Protein and Its Interaction with the RNA Subunit of Dictyostelium discoideum RNase P

Insights into functional modulation of catalytic RNA activity

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