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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. Copyright © 2016, American Association for the Advancement of Science.


Dmitry E Agafonov, Berthold Kastner, Olexandr Dybkov, Romina V Hofele, Wen-Ti Liu, Henning Urlaub, Reinhard Lührmann, Holger Stark. Molecular architecture of the human U4/U6.U5 tri-snRNP. Science (New York, N.Y.). 2016 Mar 25;351(6280):1416-20

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PMID: 26912367

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