Expression of the vault RNA protects cells from undergoing apoptosis

被引:68
作者
Amort, Melanie [1 ]
Nachbauer, Birgit [1 ,2 ,3 ]
Tuzlak, Selma [4 ]
Kieser, Arnd [5 ,6 ]
Schepers, Aloys [5 ,6 ]
Villunger, Andreas [4 ]
Polacek, Norbert [1 ,2 ]
机构
[1] Med Univ Innsbruck, Div Genom & RNom, A-6020 Innsbruck, Austria
[2] Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland
[3] Univ Bern, Grad Sch Cellular & Biomed Sci, CH-3012 Bern, Switzerland
[4] Med Univ Innsbruck, Div Dev Immunol, A-6020 Innsbruck, Austria
[5] Helmholtz Zentrum Munchen, Res Unit Gene Vectors, D-81377 Munich, Germany
[6] German Ctr Infect Res DZIF, D-81377 Munich, Germany
基金
奥地利科学基金会; 瑞士国家科学基金会;
关键词
EPSTEIN-BARR-VIRUS; CASPASE RECRUITMENT DOMAIN; NONCODING RNA; MULTIDRUG-RESISTANCE; MALIGNANT-CELLS; CANCER-CELLS; REPRESSOR; DEATH; TRANSCRIPTION; ACTIVATION;
D O I
10.1038/ncomms8030
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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-kappa B-mediated role of the non-coding vtRNA1-1 in inhibiting both the extrinsic and intrinsic apoptotic pathways.
引用
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页数:11
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