Intronic splicing enhancer

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. 

Naturally, a whole cornucopia of accessory factors regulates splicing and splice site selection [18]. In addition to cis-elements within the RNA, several families of RNA factors control which alternative splicing path is chosen. Well-studied examples include serine-rich (SR) proteins and heterologous nuclear ribonuclear particles (hnRNPs) [19, 20]. SR proteins bind to exonic splicing enhancers (ESEs) or intronic splicing enhancers (ISEs) and aid in recruiting the spliceosome itself. 

Figure 5. Model for /mns-spUdng in COT pre-mRNAs. The exons are represented by boxes, the introns by lines. The exonic splicing enhancers (ESE) are represented in exon 2 in thicker lines. The 3 acceptor site of intron I reacts with the S donor sites of introns 2 or 3 of other molecules of pre-mRNA (rrans-splicing). The organization of the mRNAs is shown at the right.

Introns are non-coding sequences that are excised from the precursor mRNA by specific cleavage in a process known as splicing. It has been postulated that the presence of introns enhances the efficiency of transcription by stabilizing the RNA structure, and that splicing increases the... 

The mode of inheritance of EPP is complex but has recently been clarified by enzymatic and molecular studies of families. Molecular analysis has identified more than 60 disabling mutations of the FECH gene that are inherited in EPP families in an autosomal dominant pattern. Within these families, FECH activities in patients with overt disease are lower than the half-normal activities in their asymptomatic relatives with the same mutation. Thus a decrease in FECH activity to less than 50% of normal appears to be essential for development of sufficient overproduction of protoporphyrin to produce symptoms. In most families, this further decrease is produced by inheritance of a low expression FECH allele trans to the severe mutation. The low expression allele is a polymorphic FECH variant present in about 10% of the Western European population. Substitution of a T nucleotide by a C nucleotide at a polymorphic site in intron 3 (IVS3-48C/T) enhances use of an alternative splice site, leading to increased formation of an unstable, untranslated mRNA and reduction of FECH expression by about 25%. This pattern of inheritance has been described as autosomal dominant with modulation by expression of the wild type of FECH allele. Uncommon autosomal recessive cases of EPP have also been reported. ... 

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