ARN

@article{,

title = {Sequence elements outside the hammerhead ribozyme catalytic core enable intracellular activity},

author = {A Khvorova and A Lescoute and E Westhof and S D Jayasena},

url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12881719},

isbn = {12881719},

year  = {2003},

date = {2003-01-01},

journal = {Nat Struct Biol},

volume = {10},

number = {9},

pages = {708-712},

abstract = {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 intracellular environments. Here we demonstrate that natural HHRzs require the presence of additional nonconserved sequence elements outside of the conserved catalytic core to enable intracellular activity. These elements may stabilize the HHRz in a catalytically active conformation via tertiary interactions. HHRzs stabilized by these interactions cleave efficiently at physiological Mg2+ concentrations and are functional in vivo. The proposed role of these tertiary interacting motifs is supported by mutational, functional, structural and molecular modeling analysis of natural HHRzs.},

note = {1072-8368 

Journal Article},

keywords = {Amino Acid Motifs  Base Sequence  Catalysis  Dose-Response Relationship, Catalytic/*chemistry  Sequence Homology, Drug  Genes, Nucleic Acid  Time Factors, Reporter  Genetic Vectors  Kinetics  Magnesium/chemistry  Molecular Sequence Data  Mutation  Nucleic Acid Conformation  Plasmids/metabolism  Protein Binding  Protein Conformation  RNA/metabolism  RNA, Unité ARN, WESTHOF},

pubstate = {published},

tppubtype = {article}

}