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Quantitative microarray profiling provides evidence against widespread coupling of alternative splicing with nonsense-mediated mRNA decay to control gene expression

Banting and Best Department of Medical Research, University of Toronto, Ontario, M5G 1L6, Canada.
Genes & Development (Impact Factor: 12.64). 02/2006; 20(2):153-8. DOI: 10.1101/gad.1382806
Source: PubMed

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.

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    • ") . Taken to - gether , these estimates correlate well with those reported for flies , worms , and human ( Rehwinkel et al . , 2005 ; Pan et al . , 2006 ; Ramani et al . , 2009 ; Weischenfeldt et al . , 2012 ) . Importantly , Kalyna et al . ( 2012 ) identified AS transcripts that contained NMD features but were immune to NMD . Unexpectedly , the majority of IR transcripts were not sensitive to NMD despite containing PTCs , downstream splice junctions , and long 39UTRs . By contrast , tr"
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    The Plant Cell 10/2013; 25(10). DOI:10.1105/tpc.113.117523 · 9.58 Impact Factor
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    • "Most predicted PTC-introducing alternative splicing events [5] appear as cellular noises produced at low level by inefficient splicing during the post-transcriptional processing independently of NMD [13] [14]. There is evidence that only a relatively small proportion of PTC containing AS gene transcripts are subjected to NMD disruption [14]. It has, in fact, been found that absence of the NMD SMG1 factor induces expression changes of only 9% of the predicted PTC-containing AS products, and only 2% of these show level changes of more than 20% [15]. "
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    • "Nonetheless, our identification of conserved NMD is interesting, although not unprecedented. It has been reported that most mammalian NMD transcripts are not under selective pressure and therefore likely to be noise (Pan et al. 2006). However, members of the SR (serine–arginine) family of splicing factors use NMD isoforms to downregulate their own translation in a homeostatic manner, and it is speculated that this strategy (regulated unproductive splicing and translation or ''RUST'') may be common to splicing factors generally (Sureau et al. 2001; Lareau et al. 2007). "
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