Flipping the Switch to an Active Spliceosome

• Published in: Cell 1999-03, Vol.96 (5), p.599-602
• Main Authors: Murray, Heather L., Jarrell, Kevin A.
• Format: Article
• Language: English
• Subjects: Cold Temperature; DEAD-box RNA Helicases; Models, Genetic; Point Mutation; RNA Nucleotidyltransferases - genetics; RNA Precursors - genetics; RNA Splicing - physiology; RNA, Small Nuclear - physiology; Saccharomyces cerevisiae Proteins; Spliceosomes - physiology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)80568-1

A spliceosome is a molecular machine that catalyzes the precise excision of an intron from a pre-messenger RNA (pre-mRNA). A spliceosome rivals a ribosome in its complexity, consisting of five RNA components and up to 50 proteins (for review, see Burge et al., 1999). Prior to intron excision, the individual components of a spliceosome assemble onto an RNA substrate. In vitro studies have led to the current model of spliceosome assembly, which depicts a highly ordered sequential process resulting in the assembly of a molecular machine that harbors all of the components necessary for catalysis but is catalytically inactive. Activation of the assembled spliceosome requires a dramatic reorganization of the assembled components. It is as though the assembled spliceosome stands poised to cleave and reconfigure its substrate but remains idle until a "switch is flipped" that activates the machine. This review will focus on two papers in the January issue of Molecular Cell (Kuhn et al., 1999; Staley and Guthrie, 1999) that contribute new insight on the identity, and mechanism of action, of components that "flip the switch" to activate the spliceosome.