Intron splicing

Genetta, T., Morisaki, H., Morisaki, T. and Holmes, E. W. A novel bipartite intronic splicing enhancer promotes the inclusion of a mini-exon in the AMP deaminase 1 gene. J. Biol. Chem. 276 25589-25597,2001. 

In the microorganismTetrahymena, group I intron splicing is accomplished in the catalytic cycle shown in Fig. 2. The intron first binds guanosine or one of its 5 -phos-phorylated derivatives which is then used as a nucleophile in cleaving the 5 splice site. 

The primary transcripts of prokaryotic and eukaryotic tRNAs are processed by the removal of sequences from each end (cleavage) and in a few cases by the removal of introns (splicing). Many bases and sugars in tRNAs are also modified mature tRNAs are replete with unusual bases not found in other nucleic acids (see Fig. 26-24). 

FIGURE 26-15 Splicing mechanism of group II introns. The chemistry is similar to that of group I intron splicing, except for the identity of the nucleophile in the first step and formation of a lariatlike intermediate, in which one branch is a 2, 5 -phosphodiester bond. 

Inactivating mutations (AG 1226, AT 1597, C/T 1831 stop, A A intron splice site) create receptors that lead to dominant forms of pseudohypoaldosteronism (PHA1) (45)... 

Figure 11.5. Mutation of intron splice sites involved in formation of a mutant allele of CYP2D6. (A) Normal intron consensus sequences of mammalian gene. (B) Mutation of the CYP2D6 splice site that moves the splice site downstream to the next 3 consensus sequence, altering the reading frame of the protein and resulting in a premature stop codon (CYP2D6 4) and a truncated, inactive protein.

Table 1 Predicted ratios of exonic and intronic splicing mutations...

Schwatze U, Starman BJ, Byers PH (1999) Redefinition of exon 7 in the COLlAl gene of type I collagen by an intron 8 spUce-donor-site mutation in a form of osteogenesis imperfecta influence of intron splice order on outcome of splice-site mutation. Am J Hum Genet 65 336-344... 

Stahley MR, Strobel SA. Structural evidence for a two-metal-ion mechanism of group I intron splicing. Science 2005 309 1587-1590. 

Adams PL, Stahley MR, GiU ML, Kosek AB, Wang J, Strobel SA. Crystal structure of a group I intron splicing intermediate. RNA 2004 10 1867-1887. 

Another layer of complexity appears to be emerging in the relationship between the HAS genes and malignancy. Splice variants for HASl are also related to poor outcome in malignant myeloma. Aberrant intronic splicing of HASl, resulting in three novel splice variants are detected in such patients, one of which correlates with reduced survival [129]. 

Figure 29.37 Self-spiictng. A ribosomal RNA precursor from Tetrahymena representative of the group I introns. splices itself in the presence of a guanosine cofactor (G. shown in green).

Aminoglycoside binding to RNA is not limited to binding to prokaryotic 165 ribo-somal RNA. These positively charged molecules interact with the HlV-1 Rev Response Element (RRE) transcriptional activator region [17] and TAR RNA [151], interfere with intron splicing [146], and bind to hammerhead ribozymes [153]. 

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