The spliceosome: caught in a web of shifting interactions.
Splicing is a crucial, ubiquitous and highly complex step in eukaryotic gene expression. The daunting complexity of the splicing reaction, although fascinating, has severely limited our understanding of its mechanistic details. Recent advances have begun to provide exciting new insights into the dynamic interactions that govern the function of the spliceosome, the multi-megadalton complex that performs splicing. An emerging paradigm is the presence of a succession of distinct conformational states, which are stabilized by an intricate network of interactions. Recent data suggest that even subtle changes in the composition of the interaction network can result in interconversion of the different conformational states, providing opportunities for regulation and proofreading of spliceosome function. Significant progress in proteomics has elucidated the protein composition of the spliceosome at different stages of assembly. Also, the increased sophistication and resolution of cryo-electron microscopy techniques, combined with high-resolution structural studies on a smaller scale, promise to create detailed images of the global structure of the spliceosome and its main components, which in turn will provide a plethora of mechanistic insights. Overall, the past two years have seen a convergence of data from different lines of research into what promises to become a holistic picture of spliceosome function.
Valadkhan
Saba
S
Center for RNA Molecular Biology, Case Western Reserve University, 10900 Euclid Avenue, Wood RT 100-8, Cleveland, OH 44106, USA. saba.valadkhan@case.edu
D000818:Animals; D001665:Binding Sites; D006801:Humans; D012313:RNA / Q000378:metabolism*; D012326:RNA Splicing / Q000502:physiology*; D017381:Spliceosomes / Q000502:physiology*
D012313:RNA