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

Alexandra M. Dedman, Yasser Majeed, Sarka Tumova, Fanning Zeng, Bhaskar Kumar, Christopher Munsch, Alan N. Bateson, Jürgen Wittmann, Hans Martin Jäck, Karen E. Porter, David J. Beech

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number30
JournalBMC Molecular Biology
Volume12
DOIs
Publication statusPublished - 12 Jul 2011
Externally publishedYes

Fingerprint

Vascular Smooth Muscle
Smooth Muscle Myocytes
Nonsense Codon
Alternative Splicing
Cycloheximide
Blood Vessels
Exons
Cell Proliferation
Kidney
Genes
Proteins

Keywords

  • Alternative splicing
  • Cationic channel
  • Nonsense-mediated decay
  • Transient receptor potential canonical 1

ASJC Scopus subject areas

  • Molecular Biology

Cite this

TRPC1 transcript variants, inefficient nonsense-mediated decay and low up-frameshift-1 in vascular smooth muscle cells. / Dedman, Alexandra M.; Majeed, Yasser; Tumova, Sarka; Zeng, Fanning; Kumar, Bhaskar; Munsch, Christopher; Bateson, Alan N.; Wittmann, Jürgen; Jäck, Hans Martin; Porter, Karen E.; Beech, David J.

In: BMC Molecular Biology, Vol. 12, 30, 12.07.2011.

Research output: Contribution to journalArticle

Dedman, AM, Majeed, Y, Tumova, S, Zeng, F, Kumar, B, Munsch, C, Bateson, AN, Wittmann, J, Jäck, HM, Porter, KE & Beech, DJ 2011, 'TRPC1 transcript variants, inefficient nonsense-mediated decay and low up-frameshift-1 in vascular smooth muscle cells', BMC Molecular Biology, vol. 12, 30. https://doi.org/10.1186/1471-2199-12-30
Dedman, Alexandra M. ; Majeed, Yasser ; Tumova, Sarka ; Zeng, Fanning ; Kumar, Bhaskar ; Munsch, Christopher ; Bateson, Alan N. ; Wittmann, Jürgen ; Jäck, Hans Martin ; Porter, Karen E. ; Beech, David J. / TRPC1 transcript variants, inefficient nonsense-mediated decay and low up-frameshift-1 in vascular smooth muscle cells. In: BMC Molecular Biology. 2011 ; Vol. 12.
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