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Mechanism of AS

Splicing process

Intron splicing is carried out by interaction of five small nuclear RNPs (U1, U2, U4, U5 and U6 snRNPs) and more than one hundred proteins on a step-by-step basis by using ATP (Figure 1). In the figure, proteins except for snRNPs are omitted.



Figure 1. Simplified schematic of intron splicing by spliceosome

Splicing regulation

Motifs regarding splice enhancing and silencing exist within and without exons. Motif sequences which enhance splicing in exon are called ESE (Exonic splicing enhancer) and those which silence splicing in exon are called ESS (Exonic splicing silencer). Motif sequences which enhance splicing in intron are called ISE (intronic splicing enhancer) and those which silence splicing in intron are called ISS (intronic splicing silencer). By the trans-acting splicing factors bound specificity with these motifs operate to snRNPs, alternative splicing occurs (Figure 2).



Figure 2. Alternatively regulated splicing by cis-elements (ESE, ESS, ISE and ISS) and trans-acting splicing factors (SR protein, hnRNP and so on)