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Growth arrest on inhibition of nonsense-mediated decay is mediated by noncoding RNA GAS5

Mourtada-Maarabouni, Mirna; Williams, Gwyn T.

Growth arrest on inhibition of nonsense-mediated decay is mediated by noncoding RNA GAS5 Thumbnail


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Abstract

Nonsense-mediated decay is a key RNA surveillance mechanism responsible for the rapid degradation of mRNAs containing premature termination codons and hence prevents the synthesis of truncated proteins. More recently, it has been shown that nonsense-mediated decay also has broader significance in controlling the expression of a significant proportion of the transcriptome. The importance of this mechanism to the mammalian cell is demonstrated by the observation that its inhibition causes growth arrest. The noncoding RNA growth arrest specific transcript 5 (GAS5) has recently been shown to play a key role in growth arrest induced by several mechanisms, including serum withdrawal and treatment with the mTOR inhibitor rapamycin. Here we show that inhibition of nonsense-mediated decay in several human lymphocyte cell lines causes growth arrest, and siRNA-mediated downregulation of GAS5 in these cells significantly alleviates the inhibitory effects observed. These observations hold true for inhibition of nonsense-mediated decay both through RNA interference and through pharmacological inhibition by aminoglycoside antibiotics gentamycin and G418. These studies have important implications for ototoxicity and nephrotoxicity caused by gentamycin and for the proposed use of NMD inhibition in treating genetic disease. This report further demonstrates the critical role played by GAS5 in the growth arrest of mammalian cells.

Citation

Mourtada-Maarabouni, M., & Williams, G. T. (2013). Growth arrest on inhibition of nonsense-mediated decay is mediated by noncoding RNA GAS5. BioMed Research International, 2013, Article 358015. https://doi.org/10.1155/2013/358015

Journal Article Type Article
Acceptance Date Sep 19, 2013
Publication Date Nov 11, 2013
Publicly Available Date May 26, 2023
Journal BioMed Research International
Print ISSN 2314-6133
Publisher Hindawi
Peer Reviewed Peer Reviewed
Volume 2013
Article Number 358015
ISBN 23146133 23146141
DOI https://doi.org/10.1155/2013/358015
Public URL https://keele-repository.worktribe.com/output/404131
Publisher URL http://www.hindawi.com/journals/bmri/2013/358015/

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