The hUPF1-NMD factor controls the cellular transcript levels of different genes of complex I of the respiratory chain

In this study the impact of hUPF1 and hUPF2 knockdown on alternative splicing (AS) isoforms of different genes encoding subunits of respiratory chain complex I and complex IV is described. As expected, loss of both hUPF1 and hUPF2 led to impairment of nonsense-mediated mRNA decay (NMD) and accumulat...

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Bibliographic Details
Published in:Biochimie 2012-12, Vol.94 (12), p.2600-2607
Main Authors: Panelli, Damiano, Lorusso, Francesca Paola, Trentadue, Raffaella, Stella, Alessandro, Sardanelli, Anna Maria, Papa, Sergio
Format: Article
Language:English
Subjects:
Alternative Splicing
Codon, Nonsense
Cytochrome-c oxidase
Electron transport
Electron transport chain
Electron Transport Complex I - genetics
Electron Transport Complex I - metabolism
Electron Transport Complex IV - genetics
Electron Transport Complex IV - metabolism
Gene expression
HeLa Cells
Humans
Isoenzymes - genetics
Isoenzymes - metabolism
Nonsense mediated decay
Nonsense Mediated mRNA Decay
Respiratory complex I
Reverse Transcriptase Polymerase Chain Reaction
RNA Interference
Trans-Activators - genetics
Transcription
Transcription Factors - genetics
Transcriptome - genetics
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Summary:In this study the impact of hUPF1 and hUPF2 knockdown on alternative splicing (AS) isoforms of different genes encoding subunits of respiratory chain complex I and complex IV is described. As expected, loss of both hUPF1 and hUPF2 led to impairment of nonsense-mediated mRNA decay (NMD) and accumulation of PTC-containing NMD substrates generated by both complex I and complex IV genes. The levels of some complex I splice variants, which did not contain PTC as well as the level of some complex I canonical transcripts were, however, affected only by hUPF1 knockdown. This finding confirms that NMD plays a role in the maintenance of the transcriptome integrity and reveals a specific impact of hUPF1 on the regulation of complex I genes. ► hUPF1/hUPF2 knockdown impact on splicing isoforms of complex I genes is described. ► hUPF1/hUPF2 knockdown affected the level of different PTC-containing isoforms. ► hUPF1 knockdown affected also the level of some complex I isoforms with no PTC. ► The hUPF1 factor shows a specific role in the splicing control of complex I genes.
ISSN:0300-9084
1638-6183
DOI:10.1016/j.biochi.2012.07.022