The spliceosome: a self-organized macromolecular machine in the nucleus?

In higher eukaryotes, the vast majority of protein-coding genes contain introns that must be removed from precursor mRNA (pre-mRNA) with great precision by the spliceosome. Spliceosomes are massive RNA–protein macromolecular machines with >100 distinct components that assemble onto nascent transcripts and are released from the mRNA after splicing. A large and longstanding body of biochemical evidence indicates that the spliceosome is constructed de novo for each round of splicing in an ordered piece-by-piece stepwise assembly. More recently, exciting advances in intracellular imaging approaches are providing new clues to understand the dynamic organization of this and other multi-component molecular machines in the nucleus. The emerging data suggest that stochastic interactions between spliceosomal proteins originate intermediate complexes that localize in the close vicinity of active genes, thus contributing to increase the local availability of the individual pieces required for assembly of functional spliceosomes on newly synthesized pre-mRNA.