Introns groups

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. ... 

Another type of intron (Group II) also undergoes self-splicing.589 590d The best known example is the last intron in the yeast mitochondrial pre-mRNA. The splicing pathway shown in Fig. 28-18B is similar chemically to that of the group I introns. However, the initial attack is not by free guanosine, but by the 2 OH of... 

A striking feature of many group II introns is that they can also attack DNA substrates (9). With assistance of intron encoded maturases or other cofactors, they can insert themselves into double-stranded DNA by TPRT. In this reaction, the intron reverse splices into one DNA strand while the endonuclease domain of the maturase cuts the second strand. The maturase then uses the cleaved target DNA as a primer for reverse transcription, which generates a DNA copy of the intron. Group II introns can catalyze more reactions than those discussed here for a more comprehensive overview on group II intron catalyzed reactions, see Reference 3. 

F. Martinez-Abarca, S. Zekri, and N. Toro, Characterization and in vivo of a Sinorhi-zobium meliloti group II intron associated with particular insertion sequences of the IS630-Tcl/IS3 retroposon superfamily. Mol. Microbiol. 28 1295-1306 (1998). 

In 1998 the REGRESS group published data, which showed that the TaqlB polymorphism in intron 1 of the cholesterol-ester transfer protein (CETP) gene predicts whether men with coronary artery disease would benefit from treatment with pravastatin or not [60]. Pravastatin therapy slowed the progression of coronary athero-... 

In eukaryotic cells, the initial mRNA copy contains homologues of both the intron and exon regions. The intron regions are then removed by enzymes located in the nucleus of the cell. Further enzymes splice the exon regions together to form the active mRNA molecules. In both groups of organisms, mature mRNA molecules then pass out of the nucleus into the cytoplasm. 

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,... 

Figure 6.1 The group I intron exon-spUcing mechanism. (Adapted with permission from Figure 1 of reference 24. Copyright 2004, with permission from Elsevier.)...

Group I intron phosphotransesterification reactions are carried out by a conserved active site that contains a set of imperfect double helices named PI through P9. (See Figure 6.4.) P1-P9 helices are organized into three domains P1-P2, P4-P6, and P3-P9. Specifically, the Tetrahymena thermophila intron contains two sets of coaxially stacked helices that overlap to create the active site. These helices reside in two domains of approximately equal size P4-P6 and P3-P9. P domains are defined as base-paired regions, whereas J domains... 

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