Leung, A. K. W., Nagai, K. & Li, J. (2011) Structure of the spliceosomal U4 snRNP core domain and its implication for snRNP biogenesis Nature 473, 536-539.
Janda, C.Y., Li, J., Oubridge, C., Hernández, H., Robinson, C. V., & Nagai, K. (2010) Recognition of a signal peptide by the signal recognition particle. Nature 465, 507-510.
Pomeranz Krummel, D.A., Oubridge, C., Leung, A.K.W., Li, J. & Nagai, K.(2009) Crystal structure of human spliceosomal U1 snRNP at 5.5 Å resolution. Nature 458, 475-480.
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Group Members
- Andrew Newman
- Christine Norman
- Chris Oubridge
- Marike van Roon
- Yasushi Kondo
- Wojciech Galej
- John Hardin
- Kelly Nguyen
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The excision of introns from mRNA precursors is catalysed by the large and dynamic RNA-protein assembly called the spliceosome. Four large RNA-protein complexes, termed U1, U2, U5 and U4/ U6 snRNPs, and numerous non-snRNP proteins assemble on mRNA precursors and are remodelled extensively to form the catalytically active spliceosome.
The catalytic core of the spliceosome consists of a highly structured RNA network formed between U2, U5 and U6 snRNAs and the conserved sequences in the pre-mRNA.
Our project aims to determine the structure of key RNA-protein and protein-protein complexes that constitute the active centre of the spliceosome so that the structure of the active centre and its catalytic mechanisms can be understood.
The human spliceosomal U1 snRNP, consisting of U1 snRNA and 10 proteins, binds the 5' exon-intron junction within messenger RNA precursors and initiates the assembly of the spliceosome (1).
We have recently determined the crystal structure of the functional core of human U1 snRNP and the U4 snRNP core domain. These structures have revealed the first detailed structure of a spliceosomal snRNP and provides important insights into the U1 snRNP function. Our project includes both relatively straightforward structure determination of protein domains and more difficult and ambitious structure determination of large protein and RNA-protein assemblies.
http://www2.mrc-lmb.cam.ac.uk/personal/kn/kiyoshi.html
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