Detailed close-ups and the big picture of spliceosomes

Abstract

The spliceosome is the huge macromolecular assembly responsible for the removal of introns from pre-mRNA transcripts. The size and complexity of this dynamic cellular machine dictate that structural analysis of the spliceosome is best served by a combination of techniques. Electron microscopy is providing a more global, albeit less detailed, view of spliceosome assemblies. X-ray crystallographers and NMR spectroscopists are steadily reporting more atomic resolution structures of individual spliceosome components and fragments. Increasingly, structures of these individual pieces in complex with binding partners are yielding insights into the interfaces that hold the entire spliceosome assembly together. Although the information arising from the various structural studies of splicing machinery has not yet fully converged into a complete model, we can expect that a detailed understanding of spliceosome structure will arise at the juncture of structural and computational modeling methods.

Figure 1

Toward a structural view of the spliceosome throughout the splicing cycle. Several macromolecular assemblies involved in the removal of an intron in pre-mRNA to generate mRNA have been visualized by EM and single particle reconstruction including snRNP complexes (U1, U5, U5:U4/U6 tri-snRNP, U4/U6 di-snRNP), splicing-related complexes (BΔU1, S. pombe U2.U5/U6, EJC) [43]) and structural intermediates of the spliceosome (A complex, B complex (2D averaged images only), C complex)

Figure 2

Towards combining structures of spliceosome components and complexes by computational modeling. As high-resolution structures of the over 100 components of the spliceosome and EM models of spliceosome complexes accumulate, computational modeling that incorporates interaction data and labeling information may allow for a detailed architectural model of the entire spliceosome.