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13 Spliceosome Structure and Function

Cindy L. Will, Reinhard Lührmann


Most eukaryotic genes are expressed as precursor mRNAs (pre-mRNAs) that are converted to mRNA by splicing, an essential step of gene expression in which noncoding sequences (introns) are removed and coding sequences (exons) are ligated together. The significance of pre-mRNA splicing has recently been bolstered by the results of genomic sequencing projects which indicate that the proteomic complexity of many higher eukaryotes is achieved in part by alternative splicing events that greatly expand the number of unique mRNAs that are generated by an organism (for review, see Graveley 2001). The bulk of what we currently know about pre-mRNA splicing has been obtained from genetic studies in both budding and fission yeast, and from biochemical studies in higher eukaryotes.

Nuclear pre-mRNA splicing is catalyzed by the spliceosome, a multi-megadalton ribonucleoprotein (RNP) machine. Two unique spliceosomes, which coexist in most eukaryotic cells, have been characterized to date (for review, see Patel and Steitz 2003). The major U2-dependent spliceosome is found in all eukaryotes and catalyzes the removal of U2-type introns, the most commonly encountered class of introns. The less abundant U12-dependent spliceosome, on the other hand, is present in only a subset of eukaryotes and splices the rare U12-type class of pre-mRNA introns (for detailed discussion, see Chapter 12). This review focuses on recent advances in our understanding of the structure and function of the major U2-dependent spliceosome, with emphasis on findings from human cells. A number of previous, excellent reviews of pre-mRNA splicing are considered background reading for this review and...

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