Expression of the vault RNA protects cells from undergoing apoptosis

• Published in: Nature communications Vol. 6; no. 1; p. 7030
• Main Authors: Amort, Melanie, Nachbauer, Birgit, Tuzlak, Selma, Kieser, Arnd, Schepers, Aloys, Villunger, Andreas, Polacek, Norbert
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.05.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 13; 13/109; 13/2; 13/89; 38/77; 38/90; 631/250/516/1909; 631/337/384; 631/80/82/23; 692/699/255/2514; 82/80; 96/31; Apoptosis; Base Sequence; Cell Line, Tumor; Cytoprotection; HEK293 Cells; Humanities and Social Sciences; Humans; Molecular Sequence Data; multidisciplinary; Mutation - genetics; Nucleic Acid Conformation; Ribonucleoproteins - metabolism; RNA - chemistry; RNA - genetics; RNA - metabolism; Science; Science (multidisciplinary); Signal Transduction; Viral Matrix Proteins - metabolism; Virus Latency
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms8030

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. Cellular functions of the vault complex, a large ribonucleoprotein assembly remain elusive. Here, the authors show that Epstein–Barr virus infection enhances the expression of the vault complex-associated RNAs, which leads to improved survival of infected cells due to the inhibition of cell apoptosis.