title: Position-dependent splicing activation and repression by SR and hnRNP proteins rely on common mechanisms.
abstract: Alternative splicing is regulated by splicing factors that modulate splice site selection. In some cases, however, splicing factors show antagonistic activities by either activating or repressing splicing. Here, we show that these opposing outcomes are based on their binding location relative to regulated 5' splice sites. SR proteins enhance splicing only when they are recruited to the exon. However, they interfere with splicing by simply relocating them to the opposite intronic side of the splice site. hnRNP splicing factors display analogous opposing activities, but in a reversed position dependence. Activation by SR or hnRNP proteins increases splice site recognition at the earliest steps of exon definition, whereas splicing repression promotes the assembly of nonproductive complexes that arrest spliceosome assembly prior to splice site pairing. Thus, SR and hnRNP splicing factors exploit similar mechanisms to positively or negatively influence splice site selection.
authors.affiliation: Institute of Virology, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Erkelenz
authors.forename: William F
authors.initials: WF
authors.lastname: Mueller
authors.forename: Melanie S
authors.initials: MS
authors.lastname: Evans
authors.forename: Anke
authors.initials: A
authors.lastname: Busch
authors.forename: Katrin
authors.initials: K
authors.lastname: Schöneweis
authors.forename: Klemens J
authors.initials: KJ
authors.lastname: Hertel
authors.forename: Heiner
authors.initials: H
authors.lastname: Schaal
mesh_terms: D005091:Exons; D006367:HeLa Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007438:Introns; D022821:RNA Splice Sites / Q000235:genetics / Q000502:physiology; D012326:RNA Splicing / Q000235:genetics / Q000502:physiology*
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D022821:RNA Splice Sites