Unexpected roles for UPF1 in HIV-1 RNA metabolism and translation
- Lara Ajamian1,2,4,
- Levon Abrahamyan1,4,
- Miroslav Milev1,2,
- Pavel V. Ivanov3,
- Andreas E. Kulozik3,
- Niels H. Gehring3, and
- Andrew J. Mouland1,2
- 1HIV-1 RNA Trafficking Laboratory, Lady Davis Institute for Medical Research–Sir Mortimer B. Davis Jewish General Hospital, Montréal, Québec H3T 1E2, Canada
- 2Department of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec H3A 2B4, Canada
- 3Department of Pediatric Oncology, Hematology and Immunology, University Children's Hospital, University of Heidelberg, 69120 Heidelberg, Germany
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↵4 These authors contributed equally to this work.
Abstract
The HIV-1 ribonucleoprotein (RNP) contains the major structural protein, pr55Gag, viral genomic RNA, as well as the host protein, Staufen1. In this report, we show that the nonsense-mediated decay (NMD) factor UPF1 is also a component of the HIV-1 RNP. We investigated the role of UPF1 in HIV-1-expressing cells. Depletion of UPF1 by siRNA resulted in a dramatic reduction in steady-state HIV-1 RNA and pr55Gag. Pr55Gag synthesis, but not the cognate genomic RNA, was efficiently rescued by expression of an siRNA-insensitive UPF1, demonstrating that UPF1 positively influences HIV-1 RNA translatability. Conversely, overexpression of UPF1 led to a dramatic up-regulation of HIV-1 expression at the RNA and protein synthesis levels. The effects of UPF1 on HIV-1 RNA stability were observed in the nucleus and cytoplasm and required ongoing translation. We also demonstrate that the effects exerted by UPF1 on HIV-1 expression were dependent on its ATPase activity, but were separable from its role in NMD and did not require interaction with UPF2.
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Footnotes
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Reprint requests to: Andrew J. Mouland, HIV-1 RNA Trafficking Laboratory, Lady Davis Institute for Medical Research–Sir Mortimer B. Davis Jewish General Hospital, 3755 Côte-Ste-Catherine Road, Montréal, Québec H3T 1E2, Canada; e-mail: andrew.mouland{at}mcgill.ca; fax: (514) 340-7502.
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.829208.
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- Received September 18, 2007.
- Accepted February 11, 2008.
- Copyright © 2008 RNA Society