The structure and function of catalytic RNAs.
ABSTRACT Before the discovery of ribozymes, RNA had been proposed to function as a catalyst, based on the discovery that RNA folded into high-ordered structures as protein did. This hypothesis was confirmed in the 1980s, after the discovery of Tetrahymena group I intron and RNase P ribozyme. There have been about ten ribozymes identified during the past thirty years, as well as the fact that ribosomes function as ribozymes. Advances have been made in understanding the structures and functions of ribozymes, with numerous crystal structures resolved in the past years. Here we review the structure-function relationship of both small and large ribozymes, especially the structural basis of their catalysis. ribozyme, structure, catalysis.
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Article: RNA structure: reading the ribosome.[show abstract] [hide abstract]
ABSTRACT: The crystal structures of the ribosome and its subunits have increased the amount of information about RNA structure by about two orders of magnitude. This is leading to an understanding of the principles of RNA folding and of the molecular interactions that underlie the functional capabilities of the ribosome and other RNA systems. Nearly all of the possible types of RNA tertiary interactions have been found in ribosomal RNA. One of these, an abundant tertiary structural motif called the A-minor interaction, has been shown to participate in both aminoacyl-transfer RNA selection and in peptidyl transferase; it may also play an important role in the structural dynamics of the ribosome.Science 10/2005; 309(5740):1508-14. · 31.20 Impact Factor
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ABSTRACT: The crystal structure of the bacterial 70S ribosome refined to 2.8 angstrom resolution reveals atomic details of its interactions with messenger RNA (mRNA) and transfer RNA (tRNA). A metal ion stabilizes a kink in the mRNA that demarcates the boundary between A and P sites, which is potentially important to prevent slippage of mRNA. Metal ions also stabilize the intersubunit interface. The interactions of E-site tRNA with the 50S subunit have both similarities and differences compared to those in the archaeal ribosome. The structure also rationalizes much biochemical and genetic data on translation.Science 10/2006; 313(5795):1935-42. · 31.20 Impact Factor
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ABSTRACT: To identify nucleotides in or near the active site, we have used a circularly permuted version of the VS ribozyme capable of cleavage and ligation to incorporate a single photoactive nucleotide analog, 4-thio- uridine, immediately downstream of the scissile bond. Exposure to UV light produced two cross-linked RNAs, in which the 4-thio-uridine was cross-linked to A756 in the 730 loop of helix VI. The cross-links formed only under conditions that support catalytic activity, suggesting that they reflect functionally relevant conformations of the RNA. One of the cross-linked RNAs contains a lariat, indicative of intramolecular cross-linking in the ligated RNA; the other is a branched molecule in which the scissile phosphodiester bond is cleaved, but occupies the same site in the ribozyme-substrate complex. These are the two forms of the RNA expected to be the ground state structures on either side of the transition state. This localization of the active site is consistent with previous mutational, biochemical and biophysical data, and provides direct evidence that the cleavage site in helix I interacts with the 730 loop in helix VI.The EMBO Journal 10/2002; 21(17):4691-8. · 9.82 Impact Factor