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U2 snRNP

Discovery

The snRNA of the U1 snRNP was isolated in the end of the 60’s (like the rest of them) and the RNA sequence was published in 1981 (Reddy et al., 1981) while the snRNP was isolated and characterized in 1983 via fractioning yeast nuclei (Kinlaw et al., 1983). Christine Guthrie, along with her colleagues, conducted the definitive studies revealing the interactions of U2 snRNP with other parts of the spliceosome (Guthrie, 1991).

Function

U2 is a snRNP that requires ATP to bind to the Spliceosome complex. In order, U2 binds the assembly after the binding of U1. The sequence of the snRNA that is a part of the U2 snRNP is complimentary to the consensus branch-point sequence in Yeast. (Fig.14.23) The binding of U2 to the spliceosome assembly is essential, and any mutation interfering with this is fatal to the yeast. The experiments that were carried out to determine the complimentary sequences in the U2 snRNA and the branch point sequence involved mutating the U2 snRNA sequence. This produced a mutant unable to bind the branch point sequence (as they would conclude) and the U2 was unable to perform its function. Once the branch point sequence was mutated to be complimentary to the mutant snRNA sequence, the functionality of the U2 snRNP was reestablished. (Guthrie, 1991)

Interactions

U2 has also been proven to interact with U6. These are base pairing interactions between the respective cnRNA molecules, which form what are called helices I & II. In Yeast, only helix I is essential for the splicing mechanism, while both helix I& II are essential in mammals. These interactions were discovered on a similar principle. Guthrie and colleagues, 1991 discovered lethal mutations in the U6 gene that altered the base pairs interacting with the U2 snRNA to form helix I. Once a complimentary U2 mutant snRNA was introduced, the yeast lived normally (Guthrie, 1991; Manley, 1993).

Figure: Fragments of human U2 snRNPs bound to RNA (Price et al., 1998)

Further information about this structure can be found here:

http://www.rcsb.org/pdb/cgi/explore.cgi?pid=11948989381240&pdbId=1A9N

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