title: A unique spatial arrangement of the snRNPs within the native spliceosome emerges from in silico studies.
abstract: The spliceosome is a mega-Dalton ribonucleoprotein (RNP) assembly that processes primary RNA transcripts, producing functional mRNA. The electron microscopy structures of the native spliceosome and of several spliceosomal subcomplexes are available; however, the spatial arrangement of the latter within the native spliceosome is not known. We designed a computational procedure to efficiently fit thousands of conformers into the spliceosome envelope. Despite the low resolution limitations, we obtained only one model that complies with the available biochemical data. Our model localizes the five small nuclear RNPs (snRNPs) mostly within the large subunit of the native spliceosome, requiring only minor conformation changes. The remaining free volume presumably accommodates additional spliceosomal components. The constituents of the active core of the spliceosome are juxtaposed, forming a continuous surface deep within the large spliceosomal cavity, which provides a sheltered environment for the splicing reaction.
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Frankenstein
authors.forename: Joseph
authors.initials: J
authors.lastname: Sperling
authors.forename: Ruth
authors.initials: R
authors.lastname: Sperling
authors.forename: Miriam
authors.initials: M
authors.lastname: Eisenstein
mesh_terms: D003198:Computer Simulation; D005656:Fungal Proteins / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry*; D017381:Spliceosomes / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D005656:Fungal Proteins; D017411:Ribonucleoproteins, Small Nuclear