UC Santa Cruz

Alternative pre-mRNA splicing is a dynamic mechanism responsible for the diversification of the transcriptome in eukaryotes. This robust mechanism is regulated by the interactions between trans acting RNA binding proteins (RBPs) and numerous cis-regulatory elements which exist on the pre-mRNA sequence. The interplay between RBPs and cis elements are integral to the definition of the protein coding sequences (exons) and mediating the spliceosome assembly on the non-coding regions (introns). One of the earliest events in spliceosome assembly on a pre-mRNA transcript occurs at the 3’ splice site (ss), where U2 small auxiliary factor 2 (U2AF2) recognizes the AG-dinucleotide, in part, defining the 3’ splice site. hnRNP A1 has also been shown to play a role in the definition of the 3’ ss through the direct interaction with U2AF2 and providing a proofreading mechanism through the binding of CG-dinucleotides displacing U2AF2 to the correct 3’ ss. Our lab has previously shown that hnRNP A1 plays a direct role in exon definition through the displacement of U2AF2 to decoy sites further upstream of the 3’ ss causing changes in splicing. We have also identified the decoy sites to which U2AF2 relocates to as Alu elements which are short interspaced nuclear elements (SINEs). Alu elements have long been characterized as disruptive agents in gene expression, however here we propose that Alu derived RNA elements may play a role as functional splicing regulators which might be responsible for the species-specific alternative splicing events we observe in the primate lineage.