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Mechanism U1 U2
U4 U5
U6 Associated
Proteins References
Introduction
Small Nuclear Ribonucleic-Protein Particles were first observed in the mid 1960s. Attardi et al., 1966 seems to be the first article to cite their existence, followed by Weinberg et al., 1967 that also mentions snRNPs. The term snRNPs (Snurps) was first coined by Weinberg and Penman in 1968. Since then the snRNAs (the RNA from each snRNP) were isolated, characterized and sequenced starting in 1974 with U1 and through the beginning of the 1980s.
With the advent of new technology, biochemists identified snRNP proteins that are associated with the snRNAs. The functions of the snRNPs were assayed and proposed. Eventually the spliceosome was identified and a mechanism for its role in the splicing reaction was determined. A mechanism for the spliceosome assembly and dissociation are now accepted.
There are 5 main snRNPs and more than 50 other proteins somehow associated with the spliceosome. The U1 snRNP binds to the splice site 5 exon to form the Commitment Complex (CC). Next U2 binds hydrolyzing an ATP forming the A Complex. In the next step, the U4/U6 and U5 complex (which forms separately) binds the A Complex to form the B1 Complex. Then U4 dissociates from U6, to allow U2 to bind U6 via 2 helices and form the B2 Complex. This is a regulatory step that occurs only if the orientation of the splicing machinery is correct.
ATP provides the energy for the first transesterification reaction, where the 2OH of a conserved intronic adenosine attacks the phosphate at the 5 splice site and produces a free 5 exon and a lariat intermediate, which is a branched species. In the second reaction, the 3OH of the 5 exon attacks the phosphate at the 3 splice site. This reaction produces a ligated mRNA and a lariat intron. The mRNA is then translated, while the intron is debranched and degraded.
Snurps snRNPs
snRNP Small Nuclear RiboNucleoprotein Particle
Spliceosome ribozyme complex that splices pre-mRNA
Saccharmoyces cerevisiae taxonomic Latin name for yeast
Figure: Branchpoint helix in yeast - ribbon and wireframe views (Smith JS, 1998)
More information about this structure may be found here:
http://www.rcsb.org/pdb/cgi/explore.cgi?job=summary&pdbId=17RA&page=0&pid=15030989861865
Home
Mechanism U1 U2
U4 U5
U6 Associated
Proteins References