Transcript Oksenberg_N_bms265ppt

Vault RNA
Nir Oksenberg
Monday, May 4th 2009
Discovery
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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
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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!