Quantitative microarray profiling provides evidence against widespread coupling of alternative splicing with nonsense-mediated mRNA decay to control gene expression.
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.
Pan
Qun
Q
Banting and Best Department of Medical Research, University of Toronto, Ontario, M5G 1L6, Canada.
Saltzman
Arneet L
AL
Kim
Yoon Ki
YK
Misquitta
Christine
C
Shai
Ofer
O
Maquat
Lynne E
LE
Frey
Brendan J
BJ
Blencowe
Benjamin J
BJ
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
D018389:Codon, Nonsense; D012333:RNA, Messenger; C484446:Rent1 protein, mouse; D015534:Trans-Activators; D020365:RNA Helicases; C101828:UPF1 protein, human