TRPC1 transcript variants, inefficient nonsense-mediated decay and low up-frameshift-1 in vascular smooth muscle cells
| Autor: | Hans-Martin Jäck, Yasser Majeed, Sarka Tumova, Alan N. Bateson, Alexandra M. Dedman, Bhaskar Kumar, Jürgen Wittmann, Karen E. Porter, Fanning Zeng, Christopher M. Munsch, David J. Beech |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
nonsense-mediated decay
Vascular smooth muscle lcsh:QH426-470 Transcription Genetic Medizinische Fakultät -ohne weitere Spezifikation Myocytes Smooth Muscle Nonsense-mediated decay Gene Expression cationic channel 030204 cardiovascular system & hematology Biology Muscle Smooth Vascular Cell Line Frameshift mutation TRPC1 03 medical and health sciences Exon 0302 clinical medicine Gene expression Humans Protein Isoforms ddc:610 lcsh:QH573-671 Molecular Biology Cells Cultured Cell Proliferation TRPC Cation Channels 030304 developmental biology 0303 health sciences lcsh:Cytology HEK 293 cells Alternative splicing Molecular biology lcsh:Genetics Alternative Splicing transient receptor potential canonical 1 Codon Nonsense Trans-Activators RNA Helicases Research Article |
| Zdroj: | BMC Molecular Biology BMC Molecular Biology, Vol 12, Iss 1, p 30 (2011) |
| ISSN: | 1471-2199 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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