Abstract

Graphic: Courtesy of Scott Stevens ASSEMBLY INSTRUCTIONS: In the penta-snRNP model, all five spliceosomal snRNPs interact with the substrate pre-mRNA as a single, discrete particle. Spliceosome assembly in yeast extracts also could occur by interaction of the U1 snRNP with the pre-mRNA, followed by a tetra-snRNP joining to form a functionally identical particle. (Reprinted with permission from Elsevier Science, Molecular Cell, 9:31-4, 2002.) In multicellular organisms, the earliest products of transcription, called pre-mRNAs, undergo a molecular makeover before shipping out to the cytoplasm, where the modified mRNAs spell out the recipe for protein synthesis. Preparing the pre-mRNA involves modifying the molecule's two ends and splicing out one or more introns in between. This splicing reaction occurs in large complexes known as spliceosomes, which consist of five small nuclear RNAs (snRNAs) called U1, U2, U4, U5, and U6, as well as various proteins. Together, these snRNAs and proteins form small nuclear ribonucleoprotein particles (snRNPs), setting the stage for splicing.1 The traditional view posits that spliceosome formation is a stepwise affair, with one snRNP binding to the pre-mRNA first, followed by the others in a temporal order. This model is widely held as dogma and described in every undergraduate molecular