title: Context-dependent regulatory mechanism of the splicing factor hnRNP L.
abstract: Splicing regulatory proteins often have distinct activities when bound to exons versus introns. However, less clear is whether variables aside from location can influence activity. HnRNP L binds to a motif present in both CD45 variable exons 4 and 5 to affect their coordinate repression. Here, we show that, in contrast to its direct repression of exon 4, hnRNP L represses exon 5 by countering the activity of a neighboring splicing enhancer. In the absence of the enhancer, hnRNP L unexpectedly activates exon inclusion. As the splice sites flanking exon 4 and 5 are distinct, we directly examined the effect of varying splice site strength on the mechanism of hnRNP L function. Remarkably, binding of hnRNP L to an exon represses strong splice sites but enhances weak splice sites. A model in which hnRNP L stabilizes snRNP binding can explain both effects in a manner determined by the inherent snRNP-substrate affinity.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038, USA.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Motta-Mena
authors.forename: Florian
authors.initials: F
authors.lastname: Heyd
authors.forename: Kristen W
authors.initials: KW
authors.lastname: Lynch
mesh_terms: D005091:Exons; D034664:Heterogeneous-Nuclear Ribonucleoprotein L / Q000502:physiology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D022821:RNA Splice Sites; D012326:RNA Splicing
chemical_list: D034664:Heterogeneous-Nuclear Ribonucleoprotein L; D022821:RNA Splice Sites; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human