Sequence elements outside the hammerhead ribozyme catalytic core enable intracellular activity

@article{Khvorova2003SequenceEO,
  title={Sequence elements outside the hammerhead ribozyme catalytic core enable intracellular activity},
  author={Anastasia Khvorova and Aur{\'e}lie Lescoute and Eric Westhof and Sumedha D. Jayasena},
  journal={Nature Structural Biology},
  year={2003},
  volume={10},
  pages={708-712}
}
The hammerhead ribozyme (HHRz) is a small, naturally occurring ribozyme that site-specifically cleaves RNA and has long been considered a potentially useful tool for gene silencing. The minimal conserved HHRz motif derived from natural sequences consists of three helices that intersect at a highly conserved catalytic core of 11 nucleotides. The presence of this motif is sufficient to support cleavage at high Mg2+ concentrations, but not at the low Mg2+ concentrations characteristic of… 
The hammerhead ribozyme: structure, catalysis, and gene regulation.
Intracellular selection of trans-cleaving hammerhead ribozymes
TLDR
Three mutants with enhanced intracellular cleaving activity compared to wide type hammerhead ribozyme were obtained and the best one, TX-2 was revealed to possess better and consistent gene knockdown ability at different positions on diverse targeted mRNA either in prokaryotic or eukaryotic cells than wild-type hammerhead Ribozyme.
Characterization of a native hammerhead ribozyme derived from schistosomes.
TLDR
A kinetic and thermodynamic characterization of an extended hammerhead sequence derived from Schistosoma mansoni is performed, suggesting the presence of at least two conformers, one cleaving with a fast rate and the other with a slow rate, and loop-loop interactions do aid in forming a more active conformation.
Restoration of Ribozyme Tertiary Contact and Function by Using a Molecular Glue for RNA.
TLDR
It is demonstrated that the rationally designed ribozyme switch enabled regulation of gene expression by Z-NCTS and was functional in mammalian cells.
Tertiary Contacts Distant from the Active Site Prime a Ribozyme for Catalysis
Hammerhead Ribozymes Against Virus and Viroid RNAs
The hammerhead ribozyme, a small catalytic motif that promotes self-cleavage of the RNAs in which it is found naturally embedded, can be manipulated to recognize and cleave specifically in trans
A database search for hammerhead ribozyme motifs.
TLDR
A database search for novel examples of this catalytic RNA, taking into consideration the recently defined structural requirements for an efficient cleavage under physiological magnesium ion concentrations, finds several hundreds of motifs in organisms of all kingdoms of life.
Functional Analysis of Hairpin Ribozyme Active Site Architecture*
TLDR
This study focuses on the network of noncovalent interactions that align nucleophilic and leaving group oxygens in the orientation required for the SN2-type reaction mechanism and orient the active site nucleobases near the reactive phosphate to facilitate catalytic chemistry.
Probing general acid catalysis in the hammerhead ribozyme.
TLDR
A functional characterization of the general acid catalysis mechanism and the role of an M(2+) cofactor therein, for the S. mansoni hammerhead and a simple method for synthesizing radiolabeled bridging-5'-phosphorothioate substrates are reported.
The structure-function dilemma of the hammerhead ribozyme.
TLDR
This work has evaluated and distilled the large body of biochemical data into a consensus set of functional groups unambiguously required for hammerhead catalysis, and established a concise set of disagreements between the structural and functional data.
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TLDR
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TLDR
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TLDR
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TLDR
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