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Expression of the vault RNA protects cells from undergoing apoptosis

Melanie Amort, Birgit Nachbauer, Selma Tuzlak, Arnd Kieser, Aloys Schepers, Andreas Villunger and Norbert Polacek ()
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Melanie Amort: Medical University Innsbruck
Birgit Nachbauer: Medical University Innsbruck
Selma Tuzlak: Medical University Innsbruck
Arnd Kieser: Research Unit Gene Vectors, Helmholtz Zentrum München
Aloys Schepers: Research Unit Gene Vectors, Helmholtz Zentrum München
Andreas Villunger: Medical University Innsbruck
Norbert Polacek: Medical University Innsbruck

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract Non-protein-coding RNAs are a functionally versatile class of transcripts exerting their biological roles on the RNA level. Recently, we demonstrated that the vault complex-associated RNAs (vtRNAs) are significantly upregulated in Epstein–Barr virus (EBV)-infected human B cells. Very little is known about the function(s) of the vtRNAs or the vault complex. Here, we individually express latent EBV-encoded proteins in B cells and identify the latent membrane protein 1 (LMP1) as trigger for vtRNA upregulation. Ectopic expression of vtRNA1-1, but not of the other vtRNA paralogues, results in an improved viral establishment and reduced apoptosis, a function located in the central domain of vtRNA1-1. Knockdown of the major vault protein has no effect on these phenotypes revealing that vtRNA1-1 and not the vault complex contributes to general cell death resistance. This study describes a NF-κB-mediated role of the non-coding vtRNA1-1 in inhibiting both the extrinsic and intrinsic apoptotic pathways.

Date: 2015
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DOI: 10.1038/ncomms8030

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