Ribozymes group 1 introns

Wikmark OG, Einvik C, De Jonckheere JF, Johansen SD. Short term sequence evolution and vertical inheritance of the Naegleria twin ribozyme group 1 intron. BMC Evol Biol. 2006 6 39. doi 10.1186/1471-2148-6-39. 

Fig. 1A-F The two-dimensional structures of various ribozymes. The ribozyme or intron portion is printed in black. The substrate or exon portion is printed in gray. Arrows indicate sites of cleavage by ribozymes A (left) the two-dimensional structure of a hammerhead ribozyme and its substrate. Outlined letters are conserved bases that are involved in catalysis right) The y-shaped structure of the hammerhead ribozyme-sub-strate complex B-F the two-dimensional structures of a hairpin ribozyme, the genomic HDV ribozyme, a group I ribozyme from Tetrahymena, a group II ribozyme from S. cer-evisiae (aiy5), and the ribozyme of RNase P from E. coli...

Figure 10.13 Phosphoryl-transfer reactions. The figure shows (a) nucleotide polymerization, (b) nucleic acid hydrolysis, (c) first cleavage of an exon-intron junction by group I ribozyme (d) and by a group II ribozyme, (e) strand transfer during transposition and (f) exon ligation during RNA splicing. (From Yang et al., 2006. Copyright 2006, with permission from Elsevier.)...

The discovery of self-splicing introns showed that RNA could catalyse chemical reactions. Yet, unlike proteins, RNA has no functional groups with pKa values and chemical properties similar to those considered to be important in protein-based enzymes. Steitz and Steitz (1993) postulated that two metal ions were essential for catalysis by ribozymes using a mechanism similar to DNA cleavage, in which a free 3 OH is produced. They proposed,... 

The intron group I ribozymes feature common secondary structure and reaction pathways. Active sites capable of catalyzing consecutive phosphodi-ester reactions produce properly spliced and circular RNAs. Ribozymes fold into a globular conformation and have solvent-inaccessible cores as quantified by Fe(II)-EDTA-induced free-radical cleavage experiments. The Tetrahy-mem group I intron ribozyme catalyzes phosphoryl transfer between guanosine and a substrate RNA strand—the exon. This ribozyme also has been proposed to use metal ions to assist in proper folding, to activate the nucleophile, and to stabilize the transition state. ... 

Figure 6.4 Secondary structure of a group I intron ribozyme. (From Figure 1 of reference 13. Reprinted with permission of AAAS.) (See color plate)...

Conserved in group I intron ribozymes. Invariant in group I intron ribozymes. 

The Cech group described an X-ray crystallographic structure of the group I intron from Tetrahymem thermophila in a Science magazine research article published in 1998 (PDB IGRZ). The 5.0-A resolution crystal structure included 247 nucleotides comprising most of the Tetrahymena thermophila intron. At this resolution, clear density for the ribozyme backbone was seen, and stacked bases were visualized as continuous tubes of electron density. 

In mid-1997 an international conference took place in Santa Cruz, USA, in which, for the first time, the exclusive topic was structural aspects of RNA molecules. A report covering this meeting contains an impressive graphic which shows the RNA structures, RNA/DNA complexes, and RNA/protein complexes contained in the brookhaven database as a function of the year of their publication [29]. Between 1988 and 1993 there were just 20. However, in 1996 alone no less than 41 structures appeared. These new dimensions were headed by the crystal structural elucidation of the first larger RNA molecule since the first crystal structure of tRNA in 1973 [30], the 48 nucleotide long hammerhead ribo-zyme (HHR) [31-33]. This landmark achievement was followed by a crystal structure analysis of the P4-P6-domain of a group I intron [34-36] and, more recently, a crystal structure of the hepatitis delta virus ribozyme [37]. 

Fig. 2. The P4-P6-domain of the group I intron of Tetrahymena thermophila. A Schematic representation of the secondary structure of the whole self-cleaving intron (modified after Cate et al. [34]). The labels for the paired regions P4 to P6 are indicated. The grey shaded region indicate the phylogenetically conserved catalytic core. The portion of the ribozyme that was crystallized is framed. B Three dimensional structure of the P4-P6 domain. Helices of the PSabc extension are packed against helices of the conserved core due to a bend of approximately 150° at one end of the molecule...

Another naturally occurring ribozyme which catalyzes phosphodiester transfer reactions is the hairpin ribozyme. The hairpin ribozyme has been the subject of a number of excellent review articles [24,25]. Several independent studies performed recently have indicated that the hairpin ribozyme has an interesting feature which distinguishes it from the aforementioned ribozymes mechanistically While the HHR, the group I intron, the HDV ribozyme and many other ribozymes that we are going to meet in this review are metalloenzymes and require divalent metal ions in their active sites for functional group activation, divalent metals ions only play a passive role (they are mainly required for cor-... 

Pyle AM (1996) Catalytic reaction mechanisms and structural features of group II intron ribozymes, p 75-107. In Eckstein F, Lilley DMJ (ed) Catalytic RNA, vol 10 Springer, Berlin Heidelberg New York... 

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