1. Vault RNA Nir Oksenberg Monday, May 4 th 2009

2. When: 1986 Where: UCLA Who: Dr. L. Rome and Dr. N. Kedersha How: Purifying rat liver coated vesicles, ovoid structures that were smaller than most coated vesicles were observed. Discovery Kedersha, N.L., et al. J Cell Biol, 1990. 110(4): p. 895-901.

3. The Vault Consists of a major vault protein (MVP) and 2 minor vault proteins During isolation, an additional species was identified. Kedersha, N.L., et al. 112(2): p. 225-35.

4. vRNA Less than 5% of mass of complex Functional rather than structural Length and number is species- specific – Rat/mouse: single vRNA 141b – Bullfrog: 2 vRNA species (89/94b) – Humans: 3 vRNAs hvg1: 98b hvg2: 88b hvg3: 88b Perhaps a 4 th !?! CBL3

5. Biogenesis Transcribed by RNA Pol III Remains untranslated Tissue specific pattern of expression Kickhoefer, V.A.,Trends Cell Biol, 1996. 6(5): p. 174-8.

6. What do vaults do? Intracellular transportation? Multi Drug Resistance (MDR)? http://robertscottbell.blogspot.com/2008/03/natural-solutions-to-drug-resistance.html

7. What about the vRNA? The stem-loop hvgs and TEP1 Knock out models – TEP1 KO – MVP KO KO TEP1 or MVP Is that all you got? Narf!

8. Friends of vRNA The Vault – MVP (LRP) – Minor protein 1: TEP1 – Minor protein 2: VPARP La autoantigen

9. Final thoughts Potential as a tool – Use as an intracellular transport – Study MDR and use as a prognostic marker Role in human disease – Dictyostelium – Cell proliferation/survival – KO models Future of vRNA – Do vaults/vRNAs play a direct role in drug resistance or are they merely a marker?

10. Quiet Pinky, I'm getting ready for tomorrow night Why? What are we going to do tomorrow night? The same thing we do every night. Try to find out what vRNAs do!