title: TRPC1 transcript variants, inefficient nonsense-mediated decay and low up-frameshift-1 in vascular smooth muscle cells.
abstract: 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.
authors.affiliation: Multidisciplinary Cardiovascular Research Centre, Institute of Membrane & Systems Biology, Faculty of Biological Sciences, Mount Preston Street, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Dedman
authors.forename: Yasser
authors.initials: Y
authors.lastname: Majeed
authors.forename: Sarka
authors.initials: S
authors.lastname: Tumova
authors.forename: Fanning
authors.initials: F
authors.lastname: Zeng
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Kumar
authors.forename: Christopher
authors.initials: C
authors.lastname: Munsch
authors.forename: Alan N
authors.initials: AN
authors.lastname: Bateson
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wittmann
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Jäck
authors.forename: Karen E
authors.initials: KE
authors.lastname: Porter
authors.forename: David J
authors.initials: DJ
authors.lastname: Beech
mesh_terms: D017398:Alternative Splicing; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D018389:Codon, Nonsense; D015870:Gene Expression; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics; D020365:RNA Helicases; D050052:TRPC Cation Channels / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D018389:Codon, Nonsense; D020033:Protein Isoforms; D050052:TRPC Cation Channels; D015534:Trans-Activators; C096351:transient receptor potential cation channel, subfamily C, member 1; D020365:RNA Helicases; C101828:UPF1 protein, human