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Science. 2002 Oct 11;298(5592):419-22. Epub 2002 Sep 12.

Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts.

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  • 1Institute of Genetic Medicine and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 858 Ross Building, 720 Rutland Avenue, Baltimore, MD 21205, USA.


The mechanism by which disruption of reading frame can influence pre-messenger RNA (pre-mRNA) processing is poorly understood. We assessed the role of factors essential for nonsense-mediated mRNA decay (NMD) in nonsense-mediated altered splicing (NAS) with the use of RNA interference (RNAi) in mammalian cells. Inhibition of rent1/hUpf1 expression abrogated both NMD and NAS of nonsense T cell receptor beta transcripts. In contrast, inhibition of rent2/hUpf2 expression did not disrupt NAS despite achieving comparable stabilization of nonsense transcripts. We also demonstrate that NAS and NMD are genetically separable functions of rent1/hUpf1. Additionally, rent1/hUpf1 enters the nucleus where it may directly influence early events in mRNA biogenesis. This provides compelling evidence that NAS relies on a component of the nonsense surveillance machinery but is not an indirect consequence of NMD.

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