Strategies for Identifying RNA Splicing Regulatory Motifs and Predicting Alternative Splicing Events
Figure 3
From Sequences to Patterns and Functional Elements
(A) AS events can be computationally inferred by spliced-sequence alignments of complete or partial mRNAs to genomic DNA. A selection of available algorithms and software is listed in Table S1. The sketch shows seven mRNAs with indicated exon junctions (for visual guidance only), the primary transcript structures of which are to be inferred from alignments to genomic DNA (the order of the mRNAs above and below the genomic DNA is the same). In the example shown, the set of mRNAs aligns to five exons (E1 to E5), and the data are consistent with two AS events: E2 alternative 3′ss splicing, and E3 skipping (skipped in the fourth mRNA from the top).
(B) Splicing-regulatory elements are distinguished depending on their location (exon or intron) and their mode of action (enhancing or silencing): 1) exonic splicing enhancer (ESE) elements; 2) exonic splicing silencer (ESS) elements; 3) intronic splicing enhancer (ISE) elements; and 4) intronic splicing silencer (ISS) elements. One can subclassify these elements whether they carry protein-coding information, act in the context of 5′ss and/or 3′ss, or are sequence-conserved across species (indicated by the presence of vertical colored bars).
(C) Often, ESE, ESS, ISE, and ISS elements do not act independently of their sequence context, but can assume antagonistic functions (enhancing versus silencing) in splicing. The color-coded example sequence elements are taken from the literature [27,28,32,38].