The Role of snRNAs in Spliceosomal Catalysis - Progress in Molecular Biology and Translational Science - page 190

CHAPTER SIX

The Role of snRNAs in
Spliceosomal Catalysis

Saba Valadkhan
Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA

Contents
1. Evolution of Eukaryotic Splicing Machines 196

2. Structural and Functional Similarities Between snRNAs and the Group II
Self-Splicing Introns 197

3. Role of snRNAs in the Spliceosomal Active Site 200

4. The Three-Dimensional Positioning of snRNAs in the Catalytic Core 203

5. An RNA-Centric View of the Active Site 205

6. Functionally Critical snRNA - Metal Ion Interactions 207

7. Catalytic Activity of the snRNAs in Isolation 210

8. The snRNAs in the Context of the Spliceosomal Active Site 213

9. The Role of Proteins in the Spliceosomal Catalytic Core 215

10. The Role of Spliceosomal Proteins in Remodeling the Catalytic Core 219

11. Concluding Remarks 221

References 222

Abstract
The spliceosomes, large ribonucleoprotein (RNP) assemblies that remove the interven-
ing sequences from pre-mRNAs, contain a large number of proteins and five small
nuclear RNAs (snRNAs). One snRNA, U6, contains highly conserved sequences that
are thought to be the functional counterparts of the RNA elements that form the active
site of self-splicing group II intron ribozymes. An in vitro-assembled, protein-free com-
plex of U6 with U2, the base-pairing partner in the spliceosomal catalytic core, can cat-
alyze a two-step splicing reaction in the absence of all other spliceosomal factors,
suggesting that the two snRNAs may form all or a large share of the spliceosomal active
site. On the other hand, several spliceosomal proteins are thought to help in the forma-
tion of functionally required RNA RNA interactions in the catalytic core. Whether they

also contribute functional groups to the spliceosomal active site, and thus whether the
spliceosomes are RNA or RNP enzymes remain uncertain.

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