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Vault RNA Nir Oksenberg Monday, May 4th 2009 Discovery • • • • 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. Kedersha, N.L., et al. J Cell Biol, 1990. 110(4): p. 895-901. 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. vRNA • Less than 5% of mass of complex • Functional rather than structural • Length and number is speciesspecific – Rat/mouse: single vRNA 141b – Bullfrog: 2 vRNA species (89/94b) – Humans: 3 vRNAs • • • • hvg1: 98b hvg2: 88b hvg3: 88b Perhaps a 4th!?! CBL3 Biogenesis • Transcribed by RNA Pol III Kickhoefer, V.A.,Trends Cell Biol, 1996. 6(5): p. 174-8. • Remains untranslated • Tissue specific pattern of expression What do vaults do? • Intracellular transportation? • Multi Drug Resistance (MDR)? http://robertscottbell.blogspot.com/2008/03/natural-solutions-to-drug-resistance.html 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! Friends of vRNA • The Vault – MVP (LRP) – Minor protein 1: TEP1 – Minor protein 2: VPARP • La autoantigen 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? 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!