The mysterious vault RNA

What is the role of the vault complex? The cell component was first described in 1986 but to date remains something of a scientific mystery. The gigantic complex is by far the largest cellular RNP identified to date; several functions have been suggested for it. These include roles in nucleocytoplasmic transport, intracellular detoxification processes and hence in multidrug resistance of cancer cells, signalling, apoptosis resistance, innate immune response, DNA damage repair and recently also in nuclear pore complex formation.

And, to make things still more obscure, what is the role of the vault RNA, so-called because it was first found associated to the vault complex? Today we know that a significant portion of vtRNA is not associated with the vault particle and the vtRNA does not seem to have a structural role, as its digestion does not alter the particle structure. This suggests that its role is functional and its association with the vault particle may be part of that function.

But what exactly is this function? NCCR researchers from the University of Bern have recently shed light onto the mystery. Looking at B-cells infected with the Epstein-Barr virus (EBV), Polacek et al. were able to show that expression of the vtRNA protects cells from undergoing apoptosis.

In previous work, they had shown that EBV infection of Burkitt lymphoma cells leads to an upregulation of different kinds of vtRNAs. Now they individually overexpressed most latent EBV-encoded proteins to check for vtRNA expression and this way identified the latent membrane protein 1 (LMP1) as trigger for vtRNA upregulation.

The upregulation renders the cells amenable to efficient EBV infection by protecting them from undergoing apoptosis. To make sure that it was really the vtRNA that is re- sponsible for the anti-apoptotic effect, they conducted knockdown experiments of the major vault protein (MVP), the principal protein component of the vault complex – virus establishment rates remained high in the knockdown cell line. While the MVP has been previously suggested to inhibit apoptosis in senescent cells, their study is the first report demonstrating general apoptotic resistance upon vtRNA expression in malignant B cells.

By Roland Fischer

Original article in Nature Communications