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Related Concept Videos

Ribozymes02:47

Ribozymes

The term ribozyme is used for RNA that can act as an enzyme. Ribozymes are mainly found in selected viruses, bacteria, plant organelles, and lower eukaryotes. Ribozymes were first discovered in 1982 when Tom Cech’s laboratory observed Group I introns acting as enzymes. This was shortly followed by the discovery of another ribozyme, Ribonulcease P, by Sid Altman’s laboratory. Both Cech and Altman received the Nobel Prize in chemistry in 1989 for their work on ribozymes.
Ribozymes can be...
Ribozymes02:47

Ribozymes

The term ribozyme is used for RNA that can act as an enzyme. Ribozymes are mainly found in selected viruses, bacteria, plant organelles, and lower eukaryotes. Ribozymes were first discovered in 1982 when Tom Cech’s laboratory observed Group I introns acting as enzymes. This was shortly followed by the discovery of another ribozyme, Ribonulcease P, by Sid Altman’s laboratory. Both Cech and Altman received the Nobel Prize in chemistry in 1989 for their work on ribozymes.
Ribozymes can be...
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation02:17

Reduction of Alkenes: Asymmetric Catalytic Hydrogenation

Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
Catalytically Perfect Enzymes01:07

Catalytically Perfect Enzymes

The theory of catalytically perfect enzymes was first proposed by W.J. Albery and J. R. Knowles in 1976. These enzymes catalyze biochemical reactions at high-speed. Their catalytic efficiency values range from 108-109 M-1s-1. These enzymes are also called 'diffusion-controlled' as the only rate-limiting step in the catalysis is that of the substrate diffusion into the active site. Examples include triose phosphate isomerase, fumarase, and superoxide dismutase.
Heterogeneous Catalysis01:22

Heterogeneous Catalysis

Heterogeneous catalysis involves a catalyst in a different phase from the reactants. It is a process where the catalyst and the reactants are in distinct phases, typically solid and gas or liquid.Most heterogeneous catalysts are metals, metal oxides, or acids. The list includes transition metals like iron (Fe), cobalt (Co), nickel (Ni), palladium (Pd), platinum (Pt), chromium (Cr), manganese (Mn), tungsten (W), silver (Ag), and copper (Cu). These metals possess partially vacant d orbitals that...
Riboswitches01:56

Riboswitches

Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...

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RNA Catalyst as a Reporter for Screening Drugs against RNA Editing in Trypanosomes
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Binary hammerhead ribozymes with improved catalytic activity.

M Vorobjeva1, M Zenkova, A Venyaminova

  • 1Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk 630090, Russia.

Oligonucleotides
|September 19, 2006
PubMed
Summary

New binary hammerhead ribozymes offer enhanced catalytic activity and stability for RNA targeting. Their design facilitates faster product dissociation and improved target accessibility, advancing gene silencing applications.

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • RNA Therapeutics

Background:

  • Hammerhead ribozymes are catalytic RNA molecules with therapeutic potential.
  • Existing designs face challenges in catalytic efficiency and stability.
  • Targeting specific mRNA sequences, like the mdr1 gene, is crucial for gene silencing.

Purpose of the Study:

  • To design and characterize novel binary hammerhead ribozymes with improved catalytic activity and nucleolytic stability.
  • To assess the efficacy of these binary ribozymes in cleaving target RNA, specifically the multiple drug resistance gene (mdr1) mRNA.
  • To explore strategies for enhancing ribozyme performance, including modifications and target binding interactions.

Main Methods:

  • Synthesis of binary ribozymes composed of two partially complementary oligoribonucleotides.
  • Incorporation of 2'-modified nucleotides and a 3'-3'-linked thymidine cap for enhanced nuclease resistance.
  • Assessment of catalytic activity under single and multiple reaction turnover conditions.
  • Evaluation of target RNA binding and cleavage, including structured regions of mdr1 mRNA.

Main Results:

  • The novel binary hammerhead ribozymes demonstrated high catalytic activity and enhanced nucleolytic stability.
  • Faster dissociation of cleavage products contributed to increased RNA cleavage activity compared to full-length analogs.
  • Incorporation of modifications and a thymidine cap significantly improved ribozyme stability.
  • An excess of one ribozyme strand facilitated target RNA unfolding and productive complex formation.

Conclusions:

  • Binary hammerhead ribozymes represent a promising design for efficient and stable RNA targeting.
  • These ribozymes show potential for applications in gene silencing and therapeutic interventions.
  • The design allows for overcoming target RNA secondary structures, enhancing therapeutic efficacy.