The STAR/GSG family protein rSLM-2 regulates the selection of alternative splice sites

We identified the rat Sam68-like mammalian protein (rSLM-2), a member of th e STAR (signal transduction and activation of RNA) protein family as a nove l splicing regulatory protein. Using the yeast two-hybrid system, coimmunop recipitations, and pull-down assays, we demonstrate that rSLM-2 interacts w ith various proteins involved in the regulation of alternative splicing, am ong them the serine/arginine-rich protein SRp30c, the splicing-associated f actor YT521-B and the scaffold attachment factor B, rSLM-2 can influence th e splicing pattern of the CD44v5, human transformer-2 beta and tau minigene s in cotransfection experiments. This effect can be reversed by rSLM-2-inte racting proteins, Employing rSLM-2 deletion variants, gel mobility shift as says, and linker scan mutations of the CD44 minigene, we show that the rSLM -2-dependent inclusion of exon v5 of the CD44 pre-mRNA is dependent on a sh ort purine-rich sequence. Because the related protein of rSLM-2, Sam68, is believed to play a role as an adapter protein during signal transduction, w e postulate that rSLM-2 is a link between signal transduction pathways and pre-mRNA processing.