TRPC1 transcript variants, inefficient nonsense-mediated decay and low up-frameshift-1 in vascular smooth muscle cells

BMC Molecular Biology

David J Beech¹  Karen E Porter²  Hans-Martin Jäck⁴  Jürgen Wittmann⁴  Alan N Bateson¹  Christopher Munsch³  Bhaskar Kumar¹  Fanning Zeng¹  Sarka Tumova¹  Yasser Majeed¹  Alexandra M Dedman¹ 

[1] Institute of Membrane & Systems Biology, Faculty of Biological Sciences, Mount Preston Street, University of Leeds, Leeds, LS2 9JT, UK;Faculty of Medicine & Health, Clarendon Way, University of Leeds, Leeds, LS2 9JT, UK;Yorkshire Heart Centre, General Infirmary at Leeds, Great George Street, Leeds, LS1 3EX, UK;Division of Molecular Immunology, Nikolaus Fiebiger-Center for Molecular Medicine, University of Erlangen-Nürnberg, Glueckstrasse 6, D-91054 Erlangen, Germany

关键词: transient receptor potential canonical 1;    cationic channel;    nonsense-mediated decay;    alternative splicing;   

Others  :  1129278
DOI  :  10.1186/1471-2199-12-30

 received in 2011-04-06, accepted in 2011-07-12,  发布年份 2011

【 摘 要 】

Background

Transient Receptor Potential Canonical 1 (TRPC1) is a widely-expressed mammalian cationic channel with functional effects that include stimulation of cardiovascular remodelling. The initial aim of this study was to investigate variation in TRPC1-encoding gene transcripts.

Results

Extensive TRPC1 transcript alternative splicing was observed, with exons 2, 3 and 5-9 frequently omitted, leading to variants containing premature termination codons. Consistent with the predicted sensitivity of such variants to nonsense-mediated decay (NMD) the variants were increased by cycloheximide. However it was notable that control of the variants by NMD was prominent in human embryonic kidney 293 cells but not human vascular smooth muscle cells. The cellular difference was attributed in part to a critical protein in NMD, up-frameshift-1 (UPF1), which was found to have low abundance in the vascular cells. Rescue of UPF1 by expression of exogenous UPF1 was found to suppress vascular smooth muscle cell proliferation.

Conclusions

The data suggest: (i) extensive NMD-sensitive transcripts of TRPC1; (ii) inefficient clearance of aberrant transcripts and enhanced proliferation of vascular smooth muscle cells in part because of low UPF1 expression.

【 授权许可】

   
2011 Dedman et al; licensee BioMed Central Ltd.

【 图 表 】

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