Separable Roles for rent1/hUpf1 in Altered Splicing and Decay of Nonsense Transcripts
- 11 October 2002
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 298 (5592), 419-422
- https://doi.org/10.1126/science.1074428
Abstract
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 β 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.Keywords
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