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SUMMARY:RNA maps pave the way for a better understanding of splicing regul
 ation - Jernej Ule
DTSTART:20110203T131000Z
DTEND:20110203T140000Z
UID:TALK29375@talks.cam.ac.uk
CONTACT:Dr Per Ola Kristensson
DESCRIPTION:Alternative pre-mRNA splicing increases the ability of our bod
 y to produce various cell types with diverse proteomes\, even though they 
 all share the same genomic sequence. Experimental studies indicate that up
  to 50% of mutations might cause disease by altering splicing. Splicing de
 cisions are instructed mainly by interactions between RNA-binding proteins
  and nascent transcripts. It is therefore necessary to elucidate these int
 eractions in order to fully understand the effects of disease-causing muta
 tions. However\, the transient nature and low abundance of nascent transcr
 ipts presented a great challenge to the experimental analysis of regulator
 y protein-RNA interactions. We have taken a three-pronged strategy to stud
 y these interactions on a genome-wide scale. We developed new computationa
 l approaches\, splicing microarray assays and a biochemical method to UV c
 ross-link and immunoprecipitate proteins bound to their target RNAs (CLIP)
 . We integrate information from these pre-mRNAs to create an RNA map\, whi
 ch identified the general principles underlying the positions where protei
 n-RNA interactions regulate splicing. Recently\, we have developed an inno
 vative approach to determine the sites of protein-RNA cross-linking with n
 ucleotide resolution (iCLIP). We used iCLIP to determine a high-resolution
  RNA map for the hnRNP C protein\, which indicated that the unique positio
 n-dependent splicing activity of this protein stems from its ability to bi
 nd RNA as a homotetramer. In addition\, we identified the RNA map of TIA p
 roteins\, which provided new insights into the kinetic model of splicing r
 egulation by evaluating the ability of these proteins to regulate splicing
  via positions distal to alternative exons. I will discuss these mechanist
 ic insights and present our current studies of protein-RNA interactions in
  neurodegeneration.
LOCATION:Entertaining Room\, Darwin College
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