Model of the regulation of 3′ alternative splicing of PGRP-LC pre-mRNA. For an alternative cassette (LCx, LCy, and LCa) to be included in the mRNA, the selector sequence (CE1 and CE2) upstream of the target exon interacts with the docking site (RE). When CE1 pairs with the docking site (left), such RNA pairing interaction functions to activate LCx splicing. In such cases, LCx is included in the mRNA because the remaining 3′ cassette LCy and LCa might be cleaved prior to polyadenylation. In this case, long variant PGRP-LCx is inhibited by suppressing the proximal 5′ splice site via the RNA structure, which also functions to sequester splicing activators away from the pre-mRNA targets. Likewise, when CE2 pairs with the docking site (RE), 3′ cassette LCy is activated (middle). Conversely, long LCa would be included if the docking site assumes a linear conformation without specific RNA pairing interactions and acts as an enhancer (right). In this case, the RE core motif could bind to activators to promote splicing of its immediately downstream 5′ splice site, thereby favoring long LCa inclusion.
