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RNA-RNA Interactions in Nuclear Pre-mRNA Splicing

Timothy W. Nilsen


The precise removal of intervening sequences from nuclear pre-mRNA is catalyzed within massive, remarkably complicated, ribonucleoprotein complexes known as spliceosomes. Although significant progress has been made in understanding the mechanism of splicing, many fundamental aspects of the process remain poorly or marginally understood; indeed, the entire cast of required spliceosomal constituents has yet to be identified. Furthermore, despite intensive effort in a variety of systems, it is not entirely clear how splice sites are selected, the mechanism of catalysis is not known, and the nature of the catalytic entity(s) itself (RNA or protein) has not been established.

Several aspects of pre-mRNA splicing have been extensively reviewed in recent years, and the reader is referred to these sources for additional literature citations and alternative perspectives (Guthrie 1994; Madhani and Guthrie 1994a; Newman 1994; Nilsen 1994; Ares and Weiser 1995; Krämer 1995, 1996; Umen and Guthrie 1995). In this chapter, I summarize our current understanding of the role of U snRNAs in pre-mRNA splicing, concentrating on research published subsequent to the comprehensive review by Sharp and co-workers in 1993 in the RNA World (Moore et al. 1993). Particular emphasis is given to (1) the puzzling plasticity of RNA–RNA interactions required for splicing, (2) the remarkable discovery of a second spliceosome in mammalian cells, (3) the long-standing question of whether nuclear pre-mRNA splicing is evolutionarily related to the mechanistically analogous splicing of Group II introns, and (4) the case for RNA catalysis.


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