Molecular architecture of the human U4/U6.U5 tri-snRNP
2016 | journal article. A publication with affiliation to the University of Göttingen.
Jump to: Cite & Linked | Documents & Media | Details | Version history
Documents & Media
Details
- Authors
- Agafonov, Dmitry E.; Kastner, Berthold; Dybkov, Olexandr; Hofele, Romina V.; Liu, Wen-Ti; Urlaub, Henning ; Lührmann, Reinhard ; Stark, Holger
- Abstract
- The U4/U6.U5 triple small nuclear ribonucleoprotein (tri-snRNP) is a major spliceosome building block. We obtained a three-dimensional structure of the 1.8-megadalton human tri-snRNP at a resolution of 7 angstroms using single-particle cryo-electron microscopy (cryo-EM). We fit all known high-resolution structures of tri-snRNP components into the EM density map and validated them by protein cross-linking. Our model reveals how the spatial organization of Brr2 RNA helicase prevents premature U4/U6 RNA unwinding in isolated human tri-snRNPs and how the ubiquitin C-terminal hydrolase-like protein Sad1 likely tethers the helicase Brr2 to its preactivation position. Comparison of our model with cryo-EM three-dimensional structures of the Saccharomyces cerevisiae tri-snRNP and Schizosaccharomyces pombe spliceosome indicates that Brr2 undergoes a marked conformational change during spliceosome activation, and that the scaffolding protein Prp8 is also rearranged to accommodate the spliceosome's catalytic RNA network.
- Issue Date
- 2016
- Status
- published
- Publisher
- Amer Assoc Advancement Science
- Journal
- Science
- ISSN
- 1095-9203; 0036-8075
- Sponsor
- Deutsche Forschungsgemeinschaft [SFB 860]