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Reports
Submitted on May 28, 2002 Separable Roles for rent1/hUpf1 in Altered Splicing and Decay of Nonsense Transcripts
1 Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 858 Ross Building, 720 Rutland Avenue, Baltimore, MD 21205, USA. * To whom correspondence should be addressed. E-mail: hdietz{at}jhmi.edu. The mechanism by which disruption of reading frame can influence 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) using RNA interference (RNAi) in mammalian cells. Inhibition of rent1/hUpf1 expression abrogated both NMD and NAS of nonsense T-cell receptor-ß (TCR-ß) 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 upon a component of the nonsense surveillance machinery but is not an indirect consequence of NMD.
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Science. ISSN 0036-8075 (print), 1095-9203 (online)
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