title: Quantitative microarray profiling provides evidence against widespread coupling of alternative splicing with nonsense-mediated mRNA decay to control gene expression.
abstract: Sequence-based analyses have predicted that approximately 35% of mammalian alternative splicing (AS) events produce premature termination codon (PTC)-containing splice variants that are targeted by the process of nonsense-mediated mRNA decay (NMD). This led to speculation that AS may often regulate gene expression by activating NMD. Using AS microarrays, we show that PTC-containing splice variants are generally produced at uniformly low levels across diverse mammalian cells and tissues, independently of the action of NMD. Our results suggest that most PTC-introducing AS events are not under positive selection pressure and therefore may not contribute important functional roles.
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, Ontario, M5G 1L6, Canada.
authors.forename: Qun
authors.initials: Q
authors.lastname: Pan
authors.forename: Arneet L
authors.initials: AL
authors.lastname: Saltzman
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Kim
authors.forename: Christine
authors.initials: C
authors.lastname: Misquitta
authors.forename: Ofer
authors.initials: O
authors.lastname: Shai
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Maquat
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Frey
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Blencowe
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D018389:Codon, Nonsense / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D020365:RNA Helicases / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators; D014162:Transfection
chemical_list: D018389:Codon, Nonsense; D012333:RNA, Messenger; C484446:Rent1 protein, mouse; D015534:Trans-Activators; D020365:RNA Helicases; C101828:UPF1 protein, human