Figure 2.

AS regulation by cis elements and trans-acting factors. The core cis sequence elements that define the exon/intron boundaries (5′ and 3′ splice sites (SS), GU-AG, polypyrimidine (Py) tract, and branch point sequence (BPS)) are poorly conserved. Additional enhancer and silencer elements in exons and in introns (ESE: exonic splicing enhancers; ESI: exonic splicing silencers; ISE: intronic splicing enhancers; ISI: intronic splicing silencers) contribute to the specificity of AS regulation. Trans-acting splicing factors, such as SR family proteins and heterogeneous nuclear ribonucleoprotein particles (hnRNPs), bind to enhancers and silencers and interact with spliceosomal components [18,19,20]. In general, SR proteins bound to enhancers facilitate exon definition, and hnRNPs inhibit this process.